{"format":{"id":"antibody","name":"Naked antibodies","blurb":"A target and an antibody format: whether the Fc is engineered to recruit killer cells, silenced to avoid them, fused to a trap, or copied as a biosimilar.","route":"/modalities/antibody/","engine":"/pipeline/engine/antibody/"},"counts":{"drugs":149,"approved":61,"phase3":44,"trials":883,"companies":127,"papers":271,"ideas":117,"eras":14},"how":{"paragraphs":["Lab-made immune proteins that lock onto one target, either blocking it or flagging the cell for destruction.","A humanised or fully human IgG binds a surface or soluble antigen; Fc engineering tunes effector function and half-life."],"from":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}],"technologies":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/","status":"standard-of-care","tldr":"Lab-made immune proteins that lock onto one target, either blocking it or flagging the cell for destruction."},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/","status":"standard-of-care","tldr":"Immune checkpoint inhibitors are antibodies against CTLA-4, PD-1 or PD-L1 that release the brakes on T cells so they attack the cancer. They are approved in more than 20 tumour types and produce lasting, sometimes curative responses that chemotherapy rarely does, but most patients do not respond and autoimmune side effects are the cost."},{"id":"cd47-blockade","kind":"technology","name":"CD47 and SIRP-alpha blockade","route":"/technologies/cd47-blockade/","status":"phase-2","tldr":"Drugs that remove the 'don't eat me' signal cancer cells show to macrophages, so the immune system's scavenger cells can engulf them; the lead programme was halted for safety."},{"id":"cd40-agonists","kind":"technology","name":"CD40 agonist antibodies","route":"/technologies/cd40-agonists/","status":"phase-2","tldr":"Antibodies that switch on CD40 on dendritic cells and macrophages to kick-start an immune response against tumours that checkpoint drugs alone cannot reach."},{"id":"monoclonal-antibody-manufacturing","kind":"technology","name":"Antibody manufacturing (CHO bioprocessing)","route":"/technologies/monoclonal-antibody-manufacturing/","status":"standard-of-care","tldr":"Antibody manufacturing means growing antibody drugs like pembrolizumab or trastuzumab in vats of engineered hamster cells, then purifying them. It is the industrial base for most modern cancer drugs."}]},"terms":[{"id":"adcc","kind":"term","name":"ADCC (antibody-dependent cellular cytotoxicity)","route":"/terms/adcc/","tldr":"In ADCC, an antibody flags a cell, and NK cells recognise the flag and kill it.","category":"Immunology"},{"id":"fc-effector","kind":"term","name":"Fc engineering / effector function","route":"/terms/fc-effector/","tldr":"Tweaking the antibody's tail to make it recruit immune cells more strongly, or not at all.","category":"Immunology"},{"id":"lymphoma-bio-lineage-antigen-cost","kind":"term","name":"What it costs to aim at a lineage antigen","route":"/terms/lymphoma-bio-lineage-antigen-cost/","tldr":"Almost every lymphoma drug that finds the cancer by a surface marker finds healthy cells carrying the same marker. The side effects are not accidents; they are the treatment working on the wrong cells, and they are predictable from the marker.","category":"Cancer biology"},{"id":"cps","kind":"term","name":"Combined positive score (CPS)","route":"/terms/cps/","tldr":"A PD-L1 score that counts stained tumour cells and immune cells together.","category":"Biomarkers"},{"id":"tmb","kind":"term","name":"Tumour mutational burden (TMB)","route":"/terms/tmb/","tldr":"How many mutations a tumour has. More mutations mean more targets for the immune system.","category":"Biomarkers"},{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/","tldr":"Microsatellite instability is the mark of a broken DNA spell-checker (loss of MLH1, MSH2, MSH6 or PMS2) that leaves thousands of mutations, so the tumour displays abnormal proteins that T cells can recognise. It is found in a fraction of colorectal and endometrial cancers and was the basis of the first tumour-agnostic approval, pembrolizumab in 2017.","category":"Biomarkers"},{"id":"irae","kind":"term","name":"Immune-related adverse events (irAEs)","route":"/terms/irae/","tldr":"Immune-related adverse events (irAEs) are the autoimmune side effects of checkpoint inhibitors: colitis, thyroid problems, rash, hepatitis, pneumonitis.","category":"Side effects"}],"engine":{"route":"/pipeline/engine/antibody/","axes":["Target","Antibody format"],"rows":49,"cols":6,"counts":{"approved":34,"development":40,"stopped":3,"unclear":0,"untried":249},"placed":119,"total":149,"pct":80},"approved":[{"drug":{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"},"brand":"Rituxan / MabThera (and biosimilars)","status":"approved","modality":"Monoclonal antibody (anti-CD20, chimeric)","cancers":[{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"},{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"marginal-zone-lymphoma","kind":"cancer","name":"Marginal zone lymphoma","route":"/cancers/marginal-zone-lymphoma/"},{"id":"nodular-lymphocyte-predominant-hodgkin-lymphoma","kind":"cancer","name":"Nodular lymphocyte-predominant Hodgkin lymphoma (nodular lymphocyte-predominant B-cell lymphoma)","route":"/cancers/nodular-lymphocyte-predominant-hodgkin-lymphoma/"}],"indications":["Relapsed follicular lymphoma; 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authorisation withdrawn 2012)"],"years":[2001],"firstYear":2001,"regions":["US","EU"],"target":{"key":"target","id":"cd52","name":"CD52","href":"/targets/cd52/"},"companies":[{"id":"sanofi","kind":"company","name":"Sanofi","route":"/companies/sanofi/"}]},{"drug":{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"},"brand":"Avastin (and biosimilars)","status":"approved","modality":"Monoclonal antibody (anti-VEGF)","cancers":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"},{"id":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"},{"id":"cervical","kind":"cancer","name":"Cervical cancer","route":"/cancers/cervical/"},{"id":"glioblastoma","kind":"cancer","name":"Glioma & glioblastoma","route":"/cancers/glioblastoma/"}],"indications":["First-line metastatic colorectal cancer with 5-FU chemotherapy","NSCLC; later ovarian, cervical, RCC, glioblastoma, HCC","Refractory mCRC with trifluridine/tipiracil (SUNLIGHT)","Platinum-resistant ovarian cancer with chemotherapy; recurrent/metastatic cervical cancer with chemotherapy","First-line stage III-IV ovarian cancer after surgery","First-line maintenance with olaparib in HRD-positive ovarian cancer","Metastatic colorectal cancer with fluoropyrimidine-based chemotherapy","First- and second-line metastatic colorectal cancer with fluoropyrimidine-based chemotherapy, only when targeted treatment or immunotherapy is unsuitable"],"years":[2004,2005,2006,2014,2018,2020,2023,2026],"firstYear":2004,"regions":["US","EU","England (NICE)"],"target":{"key":"target","id":"vegf","name":"VEGF / VEGFR","href":"/targets/vegf/"},"companies":[{"id":"anbogen-therapeutics","kind":"company","name":"Anbogen Therapeutics","route":"/companies/anbogen-therapeutics/"},{"id":"bio-thera-solutions","kind":"company","name":"Bio-Thera Solutions","route":"/companies/bio-thera-solutions/"},{"id":"biocon","kind":"company","name":"Biocon","route":"/companies/biocon/"},{"id":"biocon-biologics","kind":"company","name":"Biocon Biologics","route":"/companies/biocon-biologics/"},{"id":"gi-innovation","kind":"company","name":"GI Innovation","route":"/companies/gi-innovation/"},{"id":"hetero","kind":"company","name":"Hetero Drugs","route":"/companies/hetero/"},{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"},{"id":"samsung-bioepis","kind":"company","name":"Samsung Bioepis","route":"/companies/samsung-bioepis/"}]},{"drug":{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"},"brand":"Erbitux","status":"approved","modality":"Monoclonal antibody (anti-EGFR)","cancers":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"},{"id":"recurrent-metastatic-hnscc","kind":"cancer","name":"Recurrent or metastatic head and neck squamous cell carcinoma","route":"/cancers/recurrent-metastatic-hnscc/"},{"id":"hpv-negative-head-and-neck-cancer","kind":"cancer","name":"HPV-negative head and neck squamous cell carcinoma (including HPV-negative oropharyngeal cancer)","route":"/cancers/hpv-negative-head-and-neck-cancer/"}],"indications":["EGFR-expressing metastatic colorectal cancer (later restricted to RAS wild-type)","Head and neck squamous cell carcinoma with radiation","BRAF V600E mCRC with encorafenib","KRAS G12C mCRC with adagrasib","EGFR-expressing metastatic colorectal cancer; later restricted to RAS wild-type","Previously untreated EGFR-expressing RAS wild-type metastatic colorectal cancer with FOLFOX or FOLFIRI"],"years":[2004,2006,2017,2020,2024],"firstYear":2004,"regions":["US","EU","England (NICE)"],"target":{"key":"target","id":"egfr","name":"EGFR","href":"/targets/egfr/"},"companies":[{"id":"eli-lilly","kind":"company","name":"Eli Lilly (incl. 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(MSD)","route":"/companies/merck/"},{"id":"merck-kgaa","kind":"company","name":"Merck KGaA (EMD Serono)","route":"/companies/merck-kgaa/"}]},{"drug":{"id":"human-normal-immunoglobulin","kind":"drug","name":"Human normal immunoglobulin (IVIg)","route":"/drugs/human-normal-immunoglobulin/"},"brand":"Privigen / Kiovig","status":"approved","modality":"Pooled human polyclonal IgG antibody preparation (intravenous immunoglobulin)","cancers":[{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"},{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"}],"indications":["Replacement therapy in hypogammaglobulinaemia with recurrent bacterial infections in CLL (after failed antibiotic prophylaxis) and plateau-phase multiple myeloma (after failed pneumococcal immunisation); primary immunodeficiency"],"years":[2006],"firstYear":2006,"regions":["EU"],"companies":[{"id":"csl","kind":"company","name":"CSL 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(NICE)"],"target":{"key":"target","id":"egfr","name":"EGFR","href":"/targets/egfr/"},"companies":[{"id":"amgen","kind":"company","name":"Amgen","route":"/companies/amgen/"}]},{"drug":{"id":"bevacizumab-glioma","kind":"drug","name":"Bevacizumab (glioblastoma use)","route":"/drugs/bevacizumab-glioma/"},"brand":"Avastin","status":"approved","modality":"Monoclonal antibody (anti-VEGF)","cancers":[{"id":"glioblastoma","kind":"cancer","name":"Glioma & glioblastoma","route":"/cancers/glioblastoma/"}],"indications":["Recurrent glioblastoma (accelerated; full approval 2017)"],"years":[2009],"firstYear":2009,"regions":["US"],"target":{"key":"target","id":"vegf","name":"VEGF / VEGFR","href":"/targets/vegf/"},"companies":[{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"}]},{"drug":{"id":"ofatumumab","kind":"drug","name":"Ofatumumab","route":"/drugs/ofatumumab/"},"brand":"Arzerra","status":"approved","modality":"Monoclonal antibody (anti-CD20, fully human IgG1)","cancers":[{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"}],"indications":["CLL refractory to fludarabine and alemtuzumab (accelerated)","Previously untreated CLL with chlorambucil; later extended treatment and relapsed CLL with fludarabine and cyclophosphamide","CLL refractory to fludarabine and alemtuzumab (conditional; authorisation since withdrawn)"],"years":[2009,2010,2014],"firstYear":2009,"regions":["US","EU"],"target":{"key":"target","id":"cd20","name":"CD20","href":"/targets/cd20/"},"companies":[{"id":"genmab","kind":"company","name":"Genmab","route":"/companies/genmab/"},{"id":"novartis","kind":"company","name":"Novartis","route":"/companies/novartis/"}]},{"drug":{"id":"denosumab","kind":"drug","name":"Denosumab","route":"/drugs/denosumab/"},"brand":"Xgeva / Prolia","status":"approved","modality":"Monoclonal antibody (anti-RANKL, fully human 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(Xgeva)"],"years":[2010,2011,2013],"firstYear":2010,"regions":["US","EU"],"target":{"key":"target","id":"rankl","name":"RANK ligand (RANKL)","href":"/targets/rankl/"},"companies":[{"id":"amgen","kind":"company","name":"Amgen","route":"/companies/amgen/"}]},{"drug":{"id":"tocilizumab","kind":"drug","name":"Tocilizumab","route":"/drugs/tocilizumab/"},"brand":"Actemra","status":"approved","modality":"Monoclonal antibody (anti-IL-6 receptor, humanised IgG1)","cancers":[],"indications":["Rheumatoid arthritis (first approval)","Severe or life-threatening CAR-T-cell-induced cytokine release syndrome, age 2 and over"],"years":[2010,2017],"firstYear":2010,"regions":["US"],"target":{"key":"target","id":"il6","name":"Interleukin-6 and IL-6 receptor","href":"/targets/il6/"},"companies":[{"id":"roche-genentech","kind":"company","name":"Roche / 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IV)","route":"/cancers/advanced-melanoma/"},{"id":"stage-iii-melanoma","kind":"cancer","name":"Stage III melanoma (after surgery)","route":"/cancers/stage-iii-melanoma/"},{"id":"mucosal-melanoma","kind":"cancer","name":"Mucosal melanoma","route":"/cancers/mucosal-melanoma/"},{"id":"acral-melanoma","kind":"cancer","name":"Acral melanoma","route":"/cancers/acral-melanoma/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"}],"indications":["Metastatic melanoma","Untreated unresectable or metastatic MSI-high or dMMR colorectal cancer, with nivolumab","Untreated metastatic non-small-cell lung cancer, with nivolumab and two cycles of platinum doublet chemotherapy: not recommended"],"years":[2011,2021,2025],"firstYear":2011,"regions":["US","England (NICE)"],"target":{"key":"target","id":"ctla4","name":"CTLA-4","href":"/targets/ctla4/"},"companies":[{"id":"bms","kind":"company","name":"Bristol Myers Squibb","route":"/companies/bms/"}]},{"drug":{"id":"mogamulizumab","kind":"drug","name":"Mogamulizumab","route":"/drugs/mogamulizumab/"},"brand":"Poteligeo","status":"approved","modality":"Defucosylated anti-CCR4 monoclonal antibody","cancers":[{"id":"peripheral-t-cell-lymphoma","kind":"cancer","name":"Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)","route":"/cancers/peripheral-t-cell-lymphoma/"},{"id":"cutaneous-t-cell-lymphoma","kind":"cancer","name":"Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome)","route":"/cancers/cutaneous-t-cell-lymphoma/"}],"indications":["Relapsed CCR4+ adult T-cell leukaemia/lymphoma; later PTCL/CTCL","Relapsed/refractory mycosis fungoides or Sézary syndrome after ≥1 systemic therapy","MF/SS after ≥1 systemic therapy"],"years":[2012,2018],"firstYear":2012,"regions":["JP","US","EU"],"target":{"key":"target","id":"ccr4","name":"CCR4","href":"/targets/ccr4/"},"companies":[{"id":"kyowa-kirin","kind":"company","name":"Kyowa Kirin","route":"/companies/kyowa-kirin/"}]},{"drug":{"id":"pertuzumab","kind":"drug","name":"Pertuzumab","route":"/drugs/pertuzumab/"},"brand":"Perjeta; Phesgo (with trastuzumab, subcutaneous)","status":"approved","modality":"Monoclonal antibody (anti-HER2, dimerisation domain)","cancers":[{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"},{"id":"her2-positive-early-breast-cancer","kind":"cancer","name":"Early HER2-positive breast cancer","route":"/cancers/her2-positive-early-breast-cancer/"},{"id":"gallbladder","kind":"cancer","name":"Gallbladder cancer","route":"/cancers/gallbladder/"},{"id":"cholangiocarcinoma","kind":"cancer","name":"Biliary tract cancer (cholangiocarcinoma)","route":"/cancers/cholangiocarcinoma/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"biliary-tract-cancer","kind":"cancer","name":"Biliary tract cancer (all types)","route":"/cancers/biliary-tract-cancer/"}],"indications":["First-line HER2+ metastatic breast cancer with trastuzumab and docetaxel","Neoadjuvant HER2+ early breast cancer (accelerated; first pCR-based approval)","Adjuvant HER2+ early breast cancer at high risk of recurrence","Phesgo subcutaneous fixed-dose combination with trastuzumab"],"years":[2012,2013,2017,2020],"firstYear":2012,"regions":["US"],"target":{"key":"target","id":"her2+her3","name":"HER2 x HER3","href":"/targets/her2/"},"companies":[{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"}]},{"drug":{"id":"ziv-aflibercept","kind":"drug","name":"Ziv-aflibercept","route":"/drugs/ziv-aflibercept/"},"brand":"Zaltrap","status":"approved","modality":"Recombinant fusion protein (VEGF ligand trap)","cancers":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"}],"indications":["Metastatic colorectal cancer resistant to or progressing after oxaliplatin, with FOLFIRI","Metastatic colorectal cancer resistant to or progressing after an oxaliplatin-containing regimen, with FOLFIRI","Not recommended"],"years":[2012,2013,2014],"firstYear":2012,"regions":["US","EU","England (NICE)"],"target":{"key":"target","id":"vegf","name":"VEGF / VEGFR","href":"/targets/vegf/"},"companies":[{"id":"regeneron","kind":"company","name":"Regeneron","route":"/companies/regeneron/"},{"id":"sanofi","kind":"company","name":"Sanofi","route":"/companies/sanofi/"}]},{"drug":{"id":"obinutuzumab","kind":"drug","name":"Obinutuzumab","route":"/drugs/obinutuzumab/"},"brand":"Gazyva","status":"approved","modality":"Monoclonal antibody (anti-CD20, glycoengineered type II)","cancers":[{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"},{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"cll-treatment-naive","kind":"cancer","name":"Chronic lymphocytic 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cancer","route":"/cancers/gastric-msi-high/"},{"id":"cervical","kind":"cancer","name":"Cervical cancer","route":"/cancers/cervical/"},{"id":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"},{"id":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"},{"id":"hodgkin-lymphoma","kind":"cancer","name":"Hodgkin lymphoma","route":"/cancers/hodgkin-lymphoma/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"msi-high-colorectal","kind":"cancer","name":"Mismatch-repair deficient (MSI-high) colorectal cancer","route":"/cancers/msi-high-colorectal/"},{"id":"primary-mediastinal-b-cell-lymphoma","kind":"cancer","name":"Primary mediastinal (thymic) large B-cell 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gemcitabine and cisplatin (KEYNOTE-966)","Platinum-resistant PD-L1+ ovarian cancer; adjuvant RCC with belzutifan; with sacituzumab govitecan in 1L TNBC","Locally recurrent unresectable or metastatic TNBC, PD-L1 CPS 10 or more, with chemotherapy, no prior chemotherapy for metastatic disease (KEYNOTE-355)","Locally advanced or early-stage TNBC at high risk of recurrence: neoadjuvant with chemotherapy, then adjuvant monotherapy (KEYNOTE-522)","Untreated triple-negative locally recurrent unresectable or metastatic breast cancer with paclitaxel or nab-paclitaxel; NICE TA801 (29 June 2022) recommends it only for tumours with CPS 10 or more and immune-cell staining below 1 percent (the atezolizumab population is carved out), under a commercial arrangement","Neoadjuvant with chemotherapy then adjuvant alone for triple-negative early breast cancer at high risk of recurrence or locally advanced disease; NICE TA851 (14 December 2022) recommends within the marketing authorisation, routine 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at high risk of recurrence, neoadjuvant with platinum chemotherapy then adjuvant alone","Adjuvant treatment of non-small-cell lung cancer at high risk of recurrence after complete resection and platinum chemotherapy"],"years":[2014,2017,2018,2020,2021,2022,2023,2024,2025,2026],"firstYear":2014,"regions":["US","EU","UK","England (NICE)"],"target":{"key":"target","id":"pd1","name":"PD-1","href":"/targets/pd1/"},"companies":[{"id":"alliance-oncology","kind":"company","name":"Alliance for Clinical Trials in Oncology","route":"/companies/alliance-oncology/"},{"id":"biolinerx","kind":"company","name":"BioLineRx","route":"/companies/biolinerx/"},{"id":"gi-innovation","kind":"company","name":"GI Innovation","route":"/companies/gi-innovation/"},{"id":"gog-foundation","kind":"company","name":"GOG Foundation","route":"/companies/gog-foundation/"},{"id":"gv20-therapeutics","kind":"company","name":"GV20 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(MSD)","route":"/companies/merck/"},{"id":"precigen","kind":"company","name":"Precigen","route":"/companies/precigen/"},{"id":"qurient","kind":"company","name":"Qurient","route":"/companies/qurient/"},{"id":"salubris-biotherapeutics","kind":"company","name":"Salubris Biotherapeutics","route":"/companies/salubris-biotherapeutics/"},{"id":"teclison","kind":"company","name":"Teclison","route":"/companies/teclison/"}]},{"drug":{"id":"ramucirumab","kind":"drug","name":"Ramucirumab","route":"/drugs/ramucirumab/"},"brand":"Cyramza","status":"approved","modality":"Monoclonal antibody (anti-VEGFR2)","cancers":[{"id":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"}],"indications":["Gastric cancer; NSCLC","HCC with AFP ≥400 ng/mL after sorafenib","Locally advanced or metastatic non-small-cell lung cancer progressing after platinum-based chemotherapy, with docetaxel: not recommended"],"years":[2014,2016,2019],"firstYear":2014,"regions":["US","England (NICE)"],"target":{"key":"target","id":"vegf","name":"VEGF / VEGFR","href":"/targets/vegf/"},"companies":[{"id":"eli-lilly","kind":"company","name":"Eli Lilly (incl. 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Loxo)","route":"/companies/eli-lilly/"}]},{"drug":{"id":"avelumab","kind":"drug","name":"Avelumab","route":"/drugs/avelumab/"},"brand":"Bavencio","status":"approved","modality":"Monoclonal antibody (anti-PD-L1)","cancers":[{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"},{"id":"merkel-cell-carcinoma","kind":"cancer","name":"Merkel cell carcinoma","route":"/cancers/merkel-cell-carcinoma/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"},{"id":"tnbc-early","kind":"cancer","name":"Early triple-negative breast cancer","route":"/cancers/tnbc-early/"}],"indications":["Merkel cell carcinoma; urothelial cancer after platinum (accelerated)","Maintenance after first-line platinum in advanced urothelial cancer"],"years":[2017,2020],"firstYear":2017,"regions":["US"],"target":{"key":"target","id":"pdl1","name":"PD-L1","href":"/targets/pdl1/"},"companies":[{"id":"merck-kgaa","kind":"company","name":"Merck KGaA (EMD Serono)","route":"/companies/merck-kgaa/"},{"id":"pfizer","kind":"company","name":"Pfizer (incl. 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cancer","route":"/cancers/sclc/"},{"id":"mesothelioma","kind":"cancer","name":"Mesothelioma","route":"/cancers/mesothelioma/"},{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"}],"drugs":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"enrolled":242},{"trial":{"id":"nct04644289","kind":"trial","name":"WoO: Window of Opportunity Trial of Olaparib and Durvalumab in Histologically Proven EOC","route":"/trials/nct04644289/"},"nct":"NCT04644289","phase":"2","status":"recruiting","setting":"Window-of-opportunity Proof-of-concept, Non-randomized, Open-label Phase II Trial of Olaparib Given Alone (Cohort A) or in Combination With Durvalumab (Cohort B) Prior to Primary Debulking Surgery in Histologically Proven High-grade Epithelial Ovarian Cancer (EOC)","sponsor":"AGO Research GmbH","cancers":[{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"}],"drugs":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"}],"enrolled":60}],"registry":{"drugs":149,"recruiting":1274,"fetched":"2026-09-28"},"sideEffects":{"terms":[{"id":"irae","kind":"term","name":"Immune-related adverse events (irAEs)","route":"/terms/irae/","tldr":"Immune-related adverse events (irAEs) are the autoimmune side effects of checkpoint inhibitors: colitis, thyroid problems, rash, hepatitis, pneumonitis.","category":"Side effects","from":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"camrelizumab","kind":"drug","name":"Camrelizumab","route":"/drugs/camrelizumab/"},{"id":"tislelizumab","kind":"drug","name":"Tislelizumab","route":"/drugs/tislelizumab/"},{"id":"toripalimab","kind":"drug","name":"Toripalimab","route":"/drugs/toripalimab/"}]},{"id":"crs","kind":"term","name":"Cytokine release syndrome 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Most cases settle with a pause or dose reduction; a few, especially with checkpoint inhibitors or in already damaged livers, are serious.","category":"Side effects","from":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]}],"events":[{"group":"Rash, itching or skin reactions","drugs":14,"maxGrade3":4.8,"maxAnyGrade":34,"examples":[{"id":"avelumab","kind":"drug","name":"Avelumab","route":"/drugs/avelumab/"},{"id":"camrelizumab","kind":"drug","name":"Camrelizumab","route":"/drugs/camrelizumab/"},{"id":"cemiplimab","kind":"drug","name":"Cemiplimab","route":"/drugs/cemiplimab/"}]},{"group":"Diarrhoea","drugs":9,"maxGrade3":8,"maxAnyGrade":67,"examples":[{"id":"cemiplimab","kind":"drug","name":"Cemiplimab","route":"/drugs/cemiplimab/"},{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"},{"id":"dostarlimab","kind":"drug","name":"Dostarlimab","route":"/drugs/dostarlimab/"}]},{"group":"Infusion or injection reactions","drugs":9,"maxGrade3":32,"maxAnyGrade":77,"examples":[{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"},{"id":"daratumumab","kind":"drug","name":"Daratumumab","route":"/drugs/daratumumab/"},{"id":"dinutuximab","kind":"drug","name":"Dinutuximab (ch14.18) / dinutuximab beta","route":"/drugs/dinutuximab/"}]},{"group":"Thyroid changes","drugs":9,"maxGrade3":0.9,"maxAnyGrade":20,"examples":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"avelumab","kind":"drug","name":"Avelumab","route":"/drugs/avelumab/"},{"id":"cemiplimab","kind":"drug","name":"Cemiplimab","route":"/drugs/cemiplimab/"}]},{"group":"Tiredness (fatigue)","drugs":7,"maxAnyGrade":48,"examples":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"avelumab","kind":"drug","name":"Avelumab","route":"/drugs/avelumab/"},{"id":"cemiplimab","kind":"drug","name":"Cemiplimab","route":"/drugs/cemiplimab/"}]},{"group":"Liver inflammation or raised liver enzymes","drugs":6,"maxGrade3":13.4,"maxAnyGrade":15,"examples":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"dostarlimab","kind":"drug","name":"Dostarlimab","route":"/drugs/dostarlimab/"},{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"}]},{"group":"Lung inflammation (pneumonitis, ILD)","drugs":6,"maxGrade3":1,"maxAnyGrade":18.3,"examples":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"group":"Fever or febrile neutropenia","drugs":5,"maxGrade3":14,"maxAnyGrade":22.6,"examples":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"pertuzumab","kind":"drug","name":"Pertuzumab","route":"/drugs/pertuzumab/"}]},{"group":"Low white cells (neutropenia)","drugs":5,"maxGrade3":53,"maxAnyGrade":8,"examples":[{"id":"daratumumab","kind":"drug","name":"Daratumumab","route":"/drugs/daratumumab/"},{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"},{"id":"obinutuzumab","kind":"drug","name":"Obinutuzumab","route":"/drugs/obinutuzumab/"}]},{"group":"Nausea or vomiting","drugs":5,"maxAnyGrade":24,"examples":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"dostarlimab","kind":"drug","name":"Dostarlimab","route":"/drugs/dostarlimab/"},{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]}],"drugsWithToxicity":28},"resistance":[{"id":"pd1-blockade","drugClass":"PD-1 / PD-L1 checkpoint inhibitors","tldr":"Most patients never respond (primary resistance) and some responders relapse (acquired). The routes are loss of antigen presentation, no T cells in the tumour, and a suppressive microenvironment.","route":"/resistance/#pd1-blockade","exemplars":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"}],"mechanisms":[{"name":"Loss of antigen presentation (B2M, HLA, JAK1/2)","category":"immune-evasion","categoryLabel":"Immune evasion","how":"Mutations in B2M or HLA class I stop tumour cells displaying antigen; JAK1/2 loss removes interferon responsiveness (and PD-L1 induction).","frequency":"Acquired resistance in melanoma: ~25% JAK/B2M","route":"/resistance/#pd1-blockade-loss-of-antigen-presentation-b2m-hla-jak1-2"},{"name":"Immune-desert / excluded tumours","category":"immune-evasion","categoryLabel":"Immune evasion","how":"No pre-existing T-cell infiltrate (cold tumour) or T cells held at the margin by TGF-β and stroma.","route":"/resistance/#pd1-blockade-immune-desert-excluded-tumours"},{"name":"Alternative checkpoints (LAG-3, TIM-3, TIGIT)","category":"bypass","categoryLabel":"Bypass","how":"Exhausted T cells co-express other inhibitory receptors.","route":"/resistance/#pd1-blockade-alternative-checkpoints-lag-3-tim-3-tigit"},{"name":"Immunosuppressive myeloid cells and VEGF","category":"immune-evasion","categoryLabel":"Immune evasion","how":"MDSCs, M2 macrophages, and VEGF suppress T-cell function and dendritic-cell maturation.","route":"/resistance/#pd1-blockade-immunosuppressive-myeloid-cells-and-vegf"},{"name":"Loss of neoantigens / low TMB","category":"antigen","categoryLabel":"Antigen loss","how":"Immunoediting removes the clones that carried immunogenic mutations.","route":"/resistance/#pd1-blockade-loss-of-neoantigens-low-tmb"}],"sources":[{"label":"CheckMate 067 10-year (NEJM 2024)","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa2407417"}]},{"id":"anti-cd20","drugClass":"Anti-CD20 antibodies (rituximab, obinutuzumab)","tldr":"B-cell lymphomas escape rituximab either by stopping making CD20, which a report will only show if the relapse is rebiopsied, or by exhausting the complement and effector cells the antibody has to borrow in order to kill.","route":"/resistance/#anti-cd20","exemplars":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"},{"id":"obinutuzumab","kind":"drug","name":"Obinutuzumab","route":"/drugs/obinutuzumab/"},{"id":"glofitamab","kind":"drug","name":"Glofitamab","route":"/drugs/glofitamab/"}],"mechanisms":[{"name":"Loss or down-regulation of CD20","category":"antigen","categoryLabel":"Antigen loss","how":"Transcriptional down-regulation of MS4A1 rather than deletion: CD20 messenger RNA is lower in the negative cells than in the positive cells from the same patient.","frequency":"5 of 19 rebiopsied relapses (26.3%) in a 124-patient series; the denominator for everyone else is unknown because most relapses are not rebiopsied","route":"/resistance/#anti-cd20-loss-or-down-regulation-of-cd20"},{"name":"Trogocytosis (antigen shaving)","category":"antigen","categoryLabel":"Antigen loss","how":"Macrophages strip antibody-CD20 complexes off a living cell, lowering surface antigen without any change to the gene.","route":"/resistance/#anti-cd20-trogocytosis-antigen-shaving"},{"name":"Effector and complement exhaustion","category":"pharmacology","categoryLabel":"Pharmacology","how":"The antibody kills by borrowing complement, natural killer cells and macrophages; repeated dosing depletes complement locally and leaves the effectors refractory, so retreatment works less well even where the antigen is intact.","route":"/resistance/#anti-cd20-effector-and-complement-exhaustion"}],"sources":[{"label":"Hiraga et al., Blood 2009: CD20-negative transformation after rituximab-containing chemotherapy","url":"https://doi.org/10.1182/blood-2008-08-175208"}]},{"id":"pd1-hodgkin","drugClass":"PD-1 blockade in Hodgkin lymphoma","tldr":"Hodgkin lymphoma answers PD-1 blockade because it has genetically amplified the brake. When it stops answering, the usual explanation is not the brake but what the Reed-Sternberg cell presents to a T cell.","route":"/resistance/#pd1-hodgkin","exemplars":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"mechanisms":[{"name":"Loss of MHC class II on the Reed-Sternberg cell","category":"immune-evasion","categoryLabel":"Immune evasion","how":"Hodgkin lymphoma responds despite deficient MHC class I. Across the CheckMate 205 biopsies, class I and beta-2-microglobulin did not predict complete remission but class II did, which points at a CD4 T cell as the effector and makes class II loss the escape route.","route":"/resistance/#pd1-hodgkin-loss-of-mhc-class-ii-on-the-reed-sternberg-cell"},{"name":"CIITA rearrangement","category":"immune-evasion","categoryLabel":"Immune evasion","how":"Fusions of the master transactivator of MHC class II lower class II on the tumour cell and in the same event place the PD-1 ligands under new promoters, so one rearrangement both hides the tumour and raises the brake.","frequency":"15% of classical Hodgkin lymphomas and 38% of primary mediastinal B-cell lymphomas across 263 B-cell lymphomas","route":"/resistance/#pd1-hodgkin-ciita-rearrangement"},{"name":"Low-level 9p24.1 gain","category":"other","categoryLabel":"Other","how":"The alteration is near-universal but graded, and higher-level copy gain predicted longer progression-free survival, so the patients with least of it do least well.","frequency":"Of 108 cases, polysomy in 5, copy gain in 61 and amplification in 39","route":"/resistance/#pd1-hodgkin-low-level-9p24-1-gain"}],"sources":[{"label":"Roemer et al., J Clin Oncol 2018: MHC class II and PD-L1 predict outcome after PD-1 blockade in classical Hodgkin lymphoma","url":"https://doi.org/10.1200/JCO.2017.77.3994"}]}],"papers":[{"id":"paper-guilford-antiparasitic-acupuncture-meridian-case-series-2026","kind":"paper","name":"Cancer therapy using antiparasitic medications guided by acupuncture meridian assessment: a case series of six patients","route":"/key-papers/paper-guilford-antiparasitic-acupuncture-meridian-case-series-2026/","year":2026,"journal":"Integrative Medicine (Encinitas)","paperType":"observational","tldr":"Six patients with advanced cancers treated over a decade with antiparasitic drugs chosen by measuring electrical conductance at acupuncture points were reported to have lived longer than expected; the method has no established basis and the series has no controls.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]},{"id":"paper-powderly-fenbendazole-ivermectin-liver-injury-2026","kind":"paper","name":"Drug-induced liver injury following co-ingestion of veterinary fenbendazole and ivermectin for prostate cancer: a case report","route":"/key-papers/paper-powderly-fenbendazole-ivermectin-liver-injury-2026/","year":2026,"journal":"Cureus","paperType":"observational","tldr":"A 65-year-old man with prostate cancer took veterinary fenbendazole and ivermectin on alternate days for three months on the advice of online support groups and developed severe liver injury, which cleared six weeks after he stopped.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]},{"id":"paper-yilmaz-ivermectin-toxicity-j-appl-toxicol-2026","kind":"paper","name":"Ivermectin toxicity in humans and animals: clinical spectrum, mechanisms, and management","route":"/key-papers/paper-yilmaz-ivermectin-toxicity-j-appl-toxicol-2026/","year":2026,"journal":"Journal of Applied Toxicology","paperType":"review","tldr":"A 2026 review of how ivermectin poisons the nervous system: usually safe at approved doses, but encephalopathy, seizures, coma and death have followed high doses, and the pump that keeps it out of the brain is the key factor.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]},{"id":"paper-rockwell-ivermectin-benzimidazole-prescribing-jama-netw-open-2026","kind":"paper","name":"Ivermectin-benzimidazole prescribing following celebrity endorsement","route":"/key-papers/paper-rockwell-ivermectin-benzimidazole-prescribing-jama-netw-open-2026/","year":2026,"journal":"JAMA Network Open","paperType":"observational","tldr":"After a January 2025 podcast promoted ivermectin with a dog dewormer as a cancer cure, US prescriptions of the combination doubled overall and rose 2.6-fold among people with cancer, most steeply in the South.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]},{"id":"paper-saperstein-ivermectin-neurotoxicity-breast-cancer-2026","kind":"paper","name":"Life-threatening neurotoxicity following off-label ivermectin use in metastatic breast cancer: a case report","route":"/key-papers/paper-saperstein-ivermectin-neurotoxicity-breast-cancer-2026/","year":2026,"journal":"Postgraduate Medicine","paperType":"observational","tldr":"A 73-year-old woman with metastatic breast cancer took high doses of ivermectin after reading about it online, had seizures and stopped breathing adequately, and spent two days on a ventilator before recovering fully.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]},{"id":"paper-cheng-melanoma-ctdna-antiparasitic-front-oncol-2026","kind":"paper","name":"Metastatic melanoma with initial ctDNA decline and radiographic response during self-directed antiparasitic use: treatment effect or spontaneous regression?","route":"/key-papers/paper-cheng-melanoma-ctdna-antiparasitic-front-oncol-2026/","year":2026,"journal":"Frontiers in Oncology","paperType":"observational","tldr":"A man with metastatic melanoma who refused standard treatment and took ivermectin and fenbendazole saw his tumour markers and scans improve for a while, then worsen; his oncologists judged spontaneous immune regression at least as likely as any drug effect.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]},{"id":"paper-nci9673-part-b-nivolumab-ipilimumab-anal-cancer-morris-jco-2026","kind":"paper","name":"NCI9673 part B: randomised phase 2 study of nivolumab with or without ipilimumab in refractory metastatic anal cancer","route":"/key-papers/paper-nci9673-part-b-nivolumab-ipilimumab-anal-cancer-morris-jco-2026/","year":2026,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"Adding ipilimumab to nivolumab for metastatic anal cancer after chemotherapy did not improve response, progression-free survival or overall survival and doubled severe side effects.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"id":"paper-polargo-polatuzumab-r-gemox-dlbcl-jco-2026","kind":"paper","name":"Polatuzumab vedotin plus rituximab, gemcitabine, and oxaliplatin in relapsed or refractory diffuse large B-cell lymphoma: results from the phase III, randomized POLARGO trial","route":"/key-papers/paper-polargo-polatuzumab-r-gemox-dlbcl-jco-2026/","year":2026,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"Adding an antibody-drug conjugate to an outpatient chemotherapy pairing added seven months of median survival for people with relapsed aggressive lymphoma who could not have a transplant.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"paper-hulscher-ivermectin-mebendazole-cohort-anticancer-res-2026","kind":"paper","name":"Real-world clinical outcomes of ivermectin and mebendazole in cancer patients: results from a prospective observational cohort (with 2026 expression of concern)","route":"/key-papers/paper-hulscher-ivermectin-mebendazole-cohort-anticancer-res-2026/","year":2026,"journal":"Anticancer Research","paperType":"observational","tldr":"A telemedicine company's survey of patients it prescribed ivermectin and mebendazole reported that most felt better; the journal has attached an expression of concern while it checks whether the diagnoses, the regressions and the ethical approval can be verified.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]},{"id":"paper-inmind-tafasitamab-lenalidomide-rituximab-follicular-lancet-2026","kind":"paper","name":"Tafasitamab, lenalidomide, and rituximab in relapsed or refractory follicular lymphoma (inMIND): a global, phase 3, randomised controlled trial","route":"/key-papers/paper-inmind-tafasitamab-lenalidomide-rituximab-follicular-lancet-2026/","year":2026,"journal":"Lancet","paperType":"rct","tldr":"Adding a third antibody, directed at a different target, to the usual tablet-and-antibody pairing added about eight months before follicular lymphoma progressed again.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"},{"id":"tafasitamab","kind":"drug","name":"Tafasitamab","route":"/drugs/tafasitamab/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"paper-echo-acalabrutinib-bendamustine-rituximab-mantle-cell-jco-2025","kind":"paper","name":"Acalabrutinib plus bendamustine-rituximab in untreated mantle cell lymphoma","route":"/key-papers/paper-echo-acalabrutinib-bendamustine-rituximab-mantle-cell-jco-2025/","year":2025,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"Repeating the SHINE design with a more selective targeted tablet gave another seventeen months before relapse, and again did not extend life.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"paper-amplify-acalabrutinib-venetoclax-nejm-2025","kind":"paper","name":"AMPLIFY: fixed-duration acalabrutinib plus venetoclax, with or without obinutuzumab, versus chemo-immunotherapy in fit CLL patients","route":"/key-papers/paper-amplify-acalabrutinib-venetoclax-nejm-2025/","year":2025,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"In AMPLIFY, an all-oral, 14-month course of acalabrutinib plus venetoclax beat FCR or BR chemo-immunotherapy in fit CLL patients, offering a time-limited alternative to indefinite pills.","via":[{"id":"obinutuzumab","kind":"drug","name":"Obinutuzumab","route":"/drugs/obinutuzumab/"}]},{"id":"paper-aquila-daratumumab-smouldering-nejm-2025","kind":"paper","name":"AQUILA: daratumumab versus active monitoring in high-risk smouldering multiple myeloma","route":"/key-papers/paper-aquila-daratumumab-smouldering-nejm-2025/","year":2025,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Giving daratumumab for up to three years to people with high-risk smouldering myeloma roughly halved the risk of progressing to active myeloma or death compared with watching and waiting.","via":[{"id":"daratumumab","kind":"drug","name":"Daratumumab","route":"/drugs/daratumumab/"}]},{"id":"paper-breakwater-nejm-2025","kind":"paper","name":"BREAKWATER: encorafenib plus cetuximab with chemotherapy as first treatment for BRAF V600E-mutated colorectal cancer","route":"/key-papers/paper-breakwater-nejm-2025/","year":2025,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding a BRAF inhibitor and an EGFR antibody to first-line chemotherapy roughly doubled survival in BRAF V600E-mutated metastatic bowel cancer, one of the worst-prognosis subtypes.","via":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"paper-echelon-3-brentuximab-lenalidomide-rituximab-dlbcl-jco-2025","kind":"paper","name":"Brentuximab vedotin combination for relapsed diffuse large B-cell lymphoma","route":"/key-papers/paper-echelon-3-brentuximab-lenalidomide-rituximab-dlbcl-jco-2025/","year":2025,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"Adding a CD30-directed antibody-drug conjugate to a tablet-and-antibody pairing added about five months of median survival for heavily pretreated people with relapsed aggressive lymphoma.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"paper-c-post-adjuvant-cemiplimab-nejm-2025","kind":"paper","name":"C-POST: adjuvant cemiplimab versus placebo in high-risk cutaneous squamous cell carcinoma","route":"/key-papers/paper-c-post-adjuvant-cemiplimab-nejm-2025/","year":2025,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"A year of cemiplimab after surgery and radiotherapy for high-risk cutaneous squamous cell carcinoma cut the risk of recurrence or death by more than two thirds, the first adjuvant therapy to work in this skin cancer.","via":[{"id":"cemiplimab","kind":"drug","name":"Cemiplimab","route":"/drugs/cemiplimab/"}]},{"id":"paper-cepheus-dara-vrd-natmed-2025","kind":"paper","name":"CEPHEUS: daratumumab quadruplet for newly diagnosed myeloma patients not having a transplant, with MRD-negativity as the main endpoint","route":"/key-papers/paper-cepheus-dara-vrd-natmed-2025/","year":2025,"journal":"Nature Medicine","paperType":"rct","tldr":"In patients who were transplant-ineligible or deferred transplant, the daratumumab quadruplet raised deep-remission rates from about 39% to 61% and cut progression risk by 43%.","via":[{"id":"daratumumab","kind":"drug","name":"Daratumumab","route":"/drugs/daratumumab/"}]},{"id":"paper-checkmate-067-10-year-nejm-2025","kind":"paper","name":"CheckMate 067 at ten years: nivolumab plus ipilimumab produces long-term survival in half of patients with advanced melanoma","route":"/key-papers/paper-checkmate-067-10-year-nejm-2025/","year":2025,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Ten years after starting treatment, about half of patients with advanced melanoma treated with nivolumab plus ipilimumab were still alive, most without any further treatment, showing that immunotherapy can cure a disease that once killed most patients within a year.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"relatlimab-nivolumab","kind":"drug","name":"Relatlimab + nivolumab","route":"/drugs/relatlimab-nivolumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-checkmate-8hw-lancet-2025","kind":"paper","name":"CheckMate 8HW: nivolumab plus ipilimumab versus nivolumab alone in MSI-high metastatic colorectal cancer","route":"/key-papers/paper-checkmate-8hw-lancet-2025/","year":2025,"journal":"The Lancet","paperType":"rct","tldr":"Dual immunotherapy with nivolumab and ipilimumab delayed progression more than nivolumab alone across all lines of treatment in microsatellite-unstable colorectal cancer, with about seven in ten patients progression-free at three years.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"id":"paper-laktionov-prolgolimab-domajor-ejc-2025","kind":"paper","name":"DOMAJOR: prolgolimab with chemotherapy first line in advanced non-squamous lung cancer","route":"/key-papers/paper-laktionov-prolgolimab-domajor-ejc-2025/","year":2025,"journal":"European Journal of Cancer","paperType":"rct","tldr":"A 292-patient randomised phase 3 in Russia, China, Hungary and Slovakia in which adding the Russian PD-1 antibody prolgolimab to pemetrexed and platinum roughly halved the risk of death, with the benefit holding in PD-L1-negative tumours.","via":[{"id":"bcd-100","kind":"drug","name":"BCD-100","route":"/drugs/bcd-100/"}]},{"id":"paper-topaz-1-three-year-survival-j-hepatol-2025","kind":"paper","name":"Durvalumab plus chemotherapy in advanced biliary tract cancer: 3-year overall survival update from the phase III TOPAZ-1 study","route":"/key-papers/paper-topaz-1-three-year-survival-j-hepatol-2025/","year":2025,"journal":"Journal of Hepatology","paperType":"rct","tldr":"Three and a half years on, adding durvalumab to chemotherapy for advanced bile duct and gallbladder cancer still showed a survival edge, and about one in seven patients were alive at three years compared with one in fourteen on chemotherapy alone.","via":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"}]},{"id":"paper-emerald-1-lancet-2025","kind":"paper","name":"EMERALD-1: durvalumab with or without bevacizumab added to transarterial chemoembolisation for embolisation-eligible hepatocellular carcinoma","route":"/key-papers/paper-emerald-1-lancet-2025/","year":2025,"journal":"The Lancet","paperType":"rct","tldr":"Adding durvalumab and bevacizumab to chemoembolisation lengthened the time to progression by about seven months in liver cancer suitable for embolisation, the first systemic combination to improve on chemoembolisation alone.","via":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"},{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"}]},{"id":"paper-harmoni-2-lancet-2025","kind":"paper","name":"HARMONi-2: ivonescimab, a PD-1 x VEGF bispecific, beats pembrolizumab head-to-head in PD-L1-positive lung cancer","route":"/key-papers/paper-harmoni-2-lancet-2025/","year":2025,"journal":"The Lancet","paperType":"rct","tldr":"In the first randomised trial to beat pembrolizumab directly, a single antibody that blocks both PD-1 and VEGF nearly doubled the time to progression in PD-L1-positive lung cancer, though survival data were still immature.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint 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It is the first ctDNA-guided adjuvant trial to improve survival.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-mujumdar-ivermectin-gynaecological-cancer-2025","kind":"paper","name":"Ivermectin and gynecologic cancer: what's the data?","route":"/key-papers/paper-mujumdar-ivermectin-gynaecological-cancer-2025/","year":2025,"journal":"Gynecologic Oncology Reports","paperType":"review","tldr":"Gynaecological oncologists reviewed the evidence for ivermectin in womb, ovarian and cervical cancers, found only cell-line data, and strongly caution against using it.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]},{"id":"paper-patel-ivermectin-cancer-curr-oncol-rep-2025","kind":"paper","name":"Ivermectin in cancer treatment: should healthcare providers caution or explore its therapeutic potential?","route":"/key-papers/paper-patel-ivermectin-cancer-curr-oncol-rep-2025/","year":2025,"journal":"Current Oncology Reports","paperType":"review","tldr":"A 2025 review that weighs the laboratory promise against the absence of human trials and concludes that clinicians should counter misinformation while supporting proper trials.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]},{"id":"paper-straughn-ivermectin-hope-versus-hype-2025","kind":"paper","name":"Ivermectin treatment for gynecologic cancers: hope versus hype","route":"/key-papers/paper-straughn-ivermectin-hope-versus-hype-2025/","year":2025,"journal":"Gynecologic Oncology Reports","paperType":"review","tldr":"An editorial accompanying the gynaecological review: repurposing is legitimate and early trials deserve support, but no major oncology organisation endorses ivermectin for cancer and patients should not forgo proven treatment for it.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]},{"id":"paper-keynote-689-nejm-2025","kind":"paper","name":"KEYNOTE-689: neoadjuvant and adjuvant pembrolizumab for resectable locally advanced head and neck cancer","route":"/key-papers/paper-keynote-689-nejm-2025/","year":2025,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Giving pembrolizumab before surgery and continuing it afterwards alongside radiotherapy reduced recurrences in resectable locally advanced head and neck cancer, the first improvement in surgical treatment of the disease in two decades.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-leap-012-lancet-2025","kind":"paper","name":"LEAP-012: transarterial chemoembolisation with lenvatinib plus pembrolizumab versus placebo for unresectable non-metastatic hepatocellular carcinoma","route":"/key-papers/paper-leap-012-lancet-2025/","year":2025,"journal":"The Lancet","paperType":"rct","tldr":"Adding lenvatinib and pembrolizumab to chemoembolisation delayed progression in intermediate-stage liver cancer, the second trial to show that systemic therapy improves on embolisation alone, at the cost of more side effects.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-matterhorn-nejm-2025","kind":"paper","name":"MATTERHORN: perioperative durvalumab with FLOT chemotherapy for resectable gastric and gastro-oesophageal junction cancer","route":"/key-papers/paper-matterhorn-nejm-2025/","year":2025,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding durvalumab to perioperative FLOT chemotherapy for operable stomach cancer reduced recurrences and doubled the rate of complete pathological response, the first immunotherapy to improve outcomes in curable gastric cancer.","via":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"}]},{"id":"paper-cercek-nonoperative-management-mismatch-repair-deficient-tumours-nejm-2025","kind":"paper","name":"Nonoperative management of mismatch repair-deficient tumors","route":"/key-papers/paper-cercek-nonoperative-management-mismatch-repair-deficient-tumours-nejm-2025/","year":2025,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"The extension of the rectal dostarlimab result to every organ: 49 of 49 rectal cancers and 35 of 54 other early-stage mismatch repair-deficient cancers disappeared on six months of one drug, and 82 patients avoided surgery altogether.","via":[{"id":"dostarlimab","kind":"drug","name":"Dostarlimab","route":"/drugs/dostarlimab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint 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trial","route":"/key-papers/paper-bullock-botensilimab-balstilimab-mss-colorectal-nat-med-2024/","year":2024,"journal":"Nature Medicine","paperType":"rct","tldr":"The first immunotherapy signal in the 95 percent of bowel cancers that have always ignored it: an engineered CTLA-4 antibody plus a PD-1 antibody shrank tumours in 17 percent of 101 heavily treated patients.","via":[{"id":"balstilimab","kind":"drug","name":"Balstilimab","route":"/drugs/balstilimab/"},{"id":"botensilimab","kind":"drug","name":"Botensilimab","route":"/drugs/botensilimab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-continuum-sintilimab-nasopharyngeal-liu-lancet-2024","kind":"paper","name":"CONTINUUM: induction-concurrent chemoradiotherapy with or without sintilimab in locoregionally advanced nasopharyngeal carcinoma","route":"/key-papers/paper-continuum-sintilimab-nasopharyngeal-liu-lancet-2024/","year":2024,"journal":"The Lancet","paperType":"rct","tldr":"Adding the PD-1 antibody sintilimab to chemotherapy and radiotherapy for advanced, non-metastatic nasopharyngeal cancer raised three-year event-free survival from 76 to 86 percent, with more but manageable side effects.","via":[{"id":"sintilimab","kind":"drug","name":"Sintilimab","route":"/drugs/sintilimab/"}]},{"id":"paper-destiny-pantumor02-jco-2024","kind":"paper","name":"DESTINY-PanTumor02: trastuzumab deruxtecan in HER2-expressing solid tumours","route":"/key-papers/paper-destiny-pantumor02-jco-2024/","year":2024,"journal":"Journal of Clinical Oncology","paperType":"observational","tldr":"Across seven tumour types including endometrial, cervical and ovarian cancers, trastuzumab deruxtecan shrank tumours in about 37 percent of patients overall and 61 percent of those with the highest HER2 expression, leading to a tumour-agnostic approval.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-duo-e-jco-2023","kind":"paper","name":"DUO-E: durvalumab with carboplatin-paclitaxel and maintenance durvalumab with or without olaparib in advanced endometrial cancer","route":"/key-papers/paper-duo-e-jco-2023/","year":2024,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"Adding durvalumab to first-line chemotherapy delayed progression in advanced endometrial cancer, and adding the PARP inhibitor olaparib to durvalumab maintenance helped further in mismatch repair-proficient tumours.","via":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"}]},{"id":"paper-ev-302-nejm-2024","kind":"paper","name":"EV-302: enfortumab vedotin plus pembrolizumab replaces chemotherapy as first treatment for advanced bladder cancer","route":"/key-papers/paper-ev-302-nejm-2024/","year":2024,"journal":"New England Journal of 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2021 as people tried it against COVID-19, from about 14 a month to a rising monthly count.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]},{"id":"paper-imerge-imetelstat-mds-lancet-2024","kind":"paper","name":"IMerge: imetelstat, a telomerase inhibitor, for transfusion-dependent lower-risk MDS after erythropoietin has failed","route":"/key-papers/paper-imerge-imetelstat-mds-lancet-2024/","year":2024,"journal":"The Lancet","paperType":"rct","tldr":"In IMerge, imetelstat, the first telomerase inhibitor to reach approval, freed about 40% of heavily transfused MDS patients from transfusions for eight weeks and 28% for six months, versus 15% and 3% with placebo.","via":[{"id":"luspatercept","kind":"drug","name":"Luspatercept","route":"/drugs/luspatercept/"}]},{"id":"paper-keynote-942-lancet-2024","kind":"paper","name":"KEYNOTE-942: a personalised mRNA cancer vaccine plus pembrolizumab after melanoma surgery","route":"/key-papers/paper-keynote-942-lancet-2024/","year":2024,"journal":"The Lancet","paperType":"rct","tldr":"A vaccine custom-made from each patient's own tumour mutations, given with pembrolizumab after surgery for high-risk melanoma, reduced recurrence by about 44% compared with pembrolizumab alone in a mid-sized randomised trial, the first sign that personalised cancer vaccines can work.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-keynote-a18-os-lancet-2024","kind":"paper","name":"KEYNOTE-A18: pembrolizumab with chemoradiotherapy for locally advanced cervical cancer (overall survival)","route":"/key-papers/paper-keynote-a18-os-lancet-2024/","year":2024,"journal":"The Lancet","paperType":"rct","tldr":"The second report from KEYNOTE-A18 showed that adding pembrolizumab to chemoradiotherapy for high-risk locally advanced cervical cancer also lengthened life: 82.6% of women were alive at three years against 74.8%, a third fewer deaths.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-keynote-a18-pfs-lancet-2024","kind":"paper","name":"KEYNOTE-A18: pembrolizumab with chemoradiotherapy for locally advanced cervical cancer (progression-free survival)","route":"/key-papers/paper-keynote-a18-pfs-lancet-2024/","year":2024,"journal":"The Lancet","paperType":"rct","tldr":"Adding pembrolizumab to standard chemoradiotherapy for high-risk locally advanced cervical cancer reduced progression or death by 30%, the first systemic advance in this setting since cisplatin was added to radiotherapy in 1999.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-nadina-nejm-2024","kind":"paper","name":"NADINA: two doses of ipilimumab plus nivolumab before surgery beat a year of nivolumab after surgery in stage III melanoma","route":"/key-papers/paper-nadina-nejm-2024/","year":2024,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Giving just two cycles of combination immunotherapy before removing melanoma lymph nodes cut relapses by more than two-thirds compared with a year of standard immunotherapy after surgery, and most patients needed no further treatment.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-niagara-nejm-2024","kind":"paper","name":"NIAGARA: durvalumab before and after cystectomy for muscle-invasive bladder cancer","route":"/key-papers/paper-niagara-nejm-2024/","year":2024,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding the immunotherapy durvalumab to chemotherapy before bladder removal, and continuing it afterwards, reduced relapse and death in muscle-invasive bladder cancer, the first improvement on neoadjuvant chemotherapy in two decades.","via":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint 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microsatellite-instability-high metastatic colorectal cancer (CheckMate 8HW)","route":"/key-papers/paper-andre-checkmate-8hw-nivolumab-ipilimumab-nejm-2024/","year":2024,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Two immunotherapy drugs together kept 72 percent of patients progression-free at two years against 14 percent on chemotherapy, the largest effect size of any first-line trial in colorectal cancer.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-lu-laura-osimertinib-stage-iii-nejm-2024","kind":"paper","name":"Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC","route":"/key-papers/paper-lu-laura-osimertinib-stage-iii-nejm-2024/","year":2024,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"For stage III lung cancer with an EGFR mutation, the standard consolidation immunotherapy works poorly. LAURA gave the EGFR tablet instead and pushed median time to progression from 5.6 months to 39.1.","via":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"}]},{"id":"paper-perseus-dara-vrd-transplant-nejm-2024","kind":"paper","name":"PERSEUS: daratumumab added to bortezomib-lenalidomide-dexamethasone around autologous transplant in newly diagnosed myeloma","route":"/key-papers/paper-perseus-dara-vrd-transplant-nejm-2024/","year":2024,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding daratumumab to the standard three-drug induction, transplant and maintenance cut progression or death by 58% and pushed MRD-negativity to three-quarters of patients.","via":[{"id":"daratumumab","kind":"drug","name":"Daratumumab","route":"/drugs/daratumumab/"}]},{"id":"paper-groarke-ponsegromab-cancer-cachexia-nejm-2024","kind":"paper","name":"Ponsegromab for the Treatment of Cancer Cachexia","route":"/key-papers/paper-groarke-ponsegromab-cancer-cachexia-nejm-2024/","year":2024,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"The 2024 phase 2 trial in which an antibody blocking the hormone GDF-15 helped patients with cancer-related wasting, a third of them with pancreatic cancer, gain about two to three kilograms in twelve weeks and become more active.","via":[{"id":"ponsegromab","kind":"drug","name":"Ponsegromab","route":"/drugs/ponsegromab/"}]},{"id":"paper-swog-s1826-nivolumab-avd-nejm-2024","kind":"paper","name":"SWOG S1826: nivolumab plus AVD chemotherapy versus brentuximab-AVD for advanced Hodgkin lymphoma in adolescents and adults","route":"/key-papers/paper-swog-s1826-nivolumab-avd-nejm-2024/","year":2024,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding a PD-1 antibody to chemotherapy beat the brentuximab-based standard, with 92% of patients progression-free at two years and less nerve damage.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-halassy-self-experiment-ovt-vaccines-2024","kind":"paper","name":"The self-experiment: a virologist treated her own recurrent breast cancer with two viruses she made in her own laboratory","route":"/key-papers/paper-halassy-self-experiment-ovt-vaccines-2024/","year":2024,"journal":"Vaccines","paperType":"observational","tldr":"A virologist whose breast cancer had come back and grown into the chest muscle injected it herself with a measles vaccine strain and then a second virus, the tumour shrank enough to be removed by simple surgery, and she was free of recurrence more than three years later.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-keynote-042-tmb-mutations-ann-oncol-2023","kind":"paper","name":"Associations of tissue tumour mutational burden and mutational status with clinical outcomes in KEYNOTE-042","route":"/key-papers/paper-keynote-042-tmb-mutations-ann-oncol-2023/","year":2023,"journal":"Annals of Oncology","paperType":"rct","tldr":"In a large randomised trial of immunotherapy given alone, patients whose tumours carried more mutations did better on the drug than on chemotherapy, and patients with fewer mutations did not.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-keynote-189-407-tmb-jtocrr-2023","kind":"paper","name":"Associations of tissue tumour mutational burden and mutational status with clinical outcomes with pembrolizumab plus chemotherapy versus chemotherapy for metastatic non-small-cell lung cancer","route":"/key-papers/paper-keynote-189-407-tmb-jtocrr-2023/","year":2023,"journal":"JTO Clinical and Research Reports","paperType":"rct","tldr":"In the two trials that established the treatment most patients with lung cancer actually receive, immunotherapy added to chemotherapy, the number of mutations in the tumour predicted nothing at all.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-atezolizumab-alveolar-soft-part-sarcoma-chen-nejm-2023","kind":"paper","name":"Atezolizumab for advanced alveolar soft part sarcoma","route":"/key-papers/paper-atezolizumab-alveolar-soft-part-sarcoma-chen-nejm-2023/","year":2023,"journal":"New England Journal of Medicine","paperType":"observational","tldr":"The PD-L1 antibody atezolizumab shrank tumours in about a quarter of patients with advanced alveolar soft part sarcoma, with responses lasting years in a disease resistant to chemotherapy, and became the first approved treatment for this sarcoma.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"}]},{"id":"paper-cartitude-4-cilta-cel-nejm-2023","kind":"paper","name":"CARTITUDE-4: cilta-cel CAR-T versus standard combinations after one to three prior lines of myeloma therapy","route":"/key-papers/paper-cartitude-4-cilta-cel-nejm-2023/","year":2023,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Moving BCMA CAR-T to the second line cut the risk of progression or death by 74% compared with standard triplets, and later improved overall survival.","via":[{"id":"daratumumab","kind":"drug","name":"Daratumumab","route":"/drugs/daratumumab/"}]},{"id":"paper-checkmate-76k-nat-med-2023","kind":"paper","name":"CheckMate 76K: adjuvant nivolumab in resected stage IIB or IIC melanoma","route":"/key-papers/paper-checkmate-76k-nat-med-2023/","year":2023,"journal":"Nature Medicine","paperType":"rct","tldr":"Adjuvant nivolumab for a year after surgery cut the risk of recurrence by more than half in stage IIB and IIC melanoma, confirming the benefit seen with pembrolizumab in the same setting.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"id":"paper-codebreak-300-nejm-2023","kind":"paper","name":"CodeBreaK 300: sotorasib plus panitumumab in chemotherapy-refractory KRAS G12C colorectal cancer","route":"/key-papers/paper-codebreak-300-nejm-2023/","year":2023,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Combining a KRAS G12C inhibitor with an EGFR antibody produced responses in about a quarter of patients with heavily pretreated KRAS G12C bowel cancer, versus none with standard chemotherapy, and more than doubled the time to progression.","via":[{"id":"panitumumab","kind":"drug","name":"Panitumumab","route":"/drugs/panitumumab/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"paper-commands-luspatercept-mds-lancet-2023","kind":"paper","name":"COMMANDS: luspatercept versus epoetin alfa as first treatment for anaemia in lower-risk MDS needing transfusions","route":"/key-papers/paper-commands-luspatercept-mds-lancet-2023/","year":2023,"journal":"The Lancet","paperType":"rct","tldr":"In COMMANDS, luspatercept, a drug that frees late-stage red cell production from TGF-beta-family braking, freed 59% of transfusion-dependent MDS patients from transfusions for at least 12 weeks, against 31% with the standard erythropoietin injection.","via":[{"id":"luspatercept","kind":"drug","name":"Luspatercept","route":"/drugs/luspatercept/"}]},{"id":"paper-sigurjonsdottir-sp142-22c3-tnbc-bcr-2023","kind":"paper","name":"Comparison of SP142 and 22C3 PD-L1 assays in a population-based cohort of triple-negative breast cancer patients in the context of their clinically established scoring algorithms","route":"/key-papers/paper-sigurjonsdottir-sp142-22c3-tnbc-bcr-2023/","year":2023,"journal":"Breast Cancer Research","paperType":"observational","tldr":"In 232 Swedish early triple-negative cancers, half were PD-L1-positive by the atezolizumab test (SP142 IC 1%) but only 27% by the pembrolizumab threshold (22C3 CPS 10), and the two tests picked partly different patients.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-destiny-lung02-goto-jco-2023","kind":"paper","name":"DESTINY-Lung02: two doses of trastuzumab deruxtecan in HER2-mutant metastatic non-small-cell lung cancer","route":"/key-papers/paper-destiny-lung02-goto-jco-2023/","year":2023,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"Comparing two doses of trastuzumab deruxtecan in HER2-mutant lung cancer showed that the lower 5.4 mg/kg dose gave the same response rate of about half with far less lung toxicity, fixing the approved dose.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-dreamseq-jco-2023","kind":"paper","name":"DREAMseq (ECOG-ACRIN EA6134): sequencing dabrafenib-trametinib and nivolumab-ipilimumab in BRAF-mutant metastatic melanoma","route":"/key-papers/paper-dreamseq-jco-2023/","year":2023,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"Starting with nivolumab plus ipilimumab and switching to BRAF-MEK inhibitors at progression gave 20 percentage points better two-year survival than the reverse order in BRAF-mutant advanced melanoma, settling the question of which to use first.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"id":"paper-ck-301-101-jitc-2023","kind":"paper","name":"Efficacy and safety of cosibelimab, an anti-PD-L1 antibody, in metastatic cutaneous squamous cell carcinoma","route":"/key-papers/paper-ck-301-101-jitc-2023/","year":2023,"journal":"Journal for ImmunoTherapy of Cancer","paperType":"observational","tldr":"The primary report of the metastatic cohort of CK-301-101: cosibelimab shrank tumours in 37 of 78 patients, most responses were still going at the cut-off, and severe immune side effects were uncommon.","via":[{"id":"cosibelimab","kind":"drug","name":"Cosibelimab","route":"/drugs/cosibelimab/"}]},{"id":"paper-glow-zolbetuximab-nat-med-2023","kind":"paper","name":"GLOW: zolbetuximab plus CAPOX in claudin 18.2-positive, HER2-negative gastric or gastro-oesophageal junction adenocarcinoma","route":"/key-papers/paper-glow-zolbetuximab-nat-med-2023/","year":2023,"journal":"Nature Medicine","paperType":"rct","tldr":"Adding the claudin 18.2 antibody zolbetuximab to CAPOX chemotherapy lengthened survival in claudin 18.2-positive advanced gastric cancer, confirming the SPOTLIGHT result with a different chemotherapy backbone.","via":[{"id":"zolbetuximab","kind":"drug","name":"Zolbetuximab","route":"/drugs/zolbetuximab/"}]},{"id":"paper-imbrave050-lancet-2023","kind":"paper","name":"IMbrave050: adjuvant atezolizumab plus bevacizumab versus active surveillance after resection or ablation of high-risk hepatocellular carcinoma","route":"/key-papers/paper-imbrave050-lancet-2023/","year":2023,"journal":"The Lancet","paperType":"rct","tldr":"A year of atezolizumab plus bevacizumab after surgery or ablation for high-risk liver cancer initially reduced recurrences, but the benefit disappeared with longer follow-up, so there is still no proven adjuvant therapy.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"}]},{"id":"paper-keynote-483-lancet-2023","kind":"paper","name":"KEYNOTE-483 (CCTG IND.227): pembrolizumab plus chemotherapy versus chemotherapy in untreated pleural mesothelioma","route":"/key-papers/paper-keynote-483-lancet-2023/","year":2023,"journal":"The Lancet","paperType":"rct","tldr":"Adding pembrolizumab to platinum-pemetrexed chemotherapy lengthened survival in untreated pleural mesothelioma by about a year in non-epithelioid tumours and by a smaller margin overall, giving a chemo-immunotherapy option alongside nivolumab-ipilimumab.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-keynote-811-janjigian-lancet-2023","kind":"paper","name":"KEYNOTE-811: pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma","route":"/key-papers/paper-keynote-811-janjigian-lancet-2023/","year":2023,"journal":"The Lancet","paperType":"rct","tldr":"Adding pembrolizumab to trastuzumab and chemotherapy improved response and progression-free survival in HER2-positive advanced gastric cancer, with the benefit concentrated in tumours that also express PD-L1.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-keynote-859-lancet-oncol-2023","kind":"paper","name":"KEYNOTE-859: pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer","route":"/key-papers/paper-keynote-859-lancet-oncol-2023/","year":2023,"journal":"The Lancet Oncology","paperType":"rct","tldr":"Adding pembrolizumab to platinum-fluoropyrimidine chemotherapy lengthened survival in HER2-negative advanced gastric cancer, with the largest gain in tumours with a PD-L1 combined positive score of 10 or more, confirming chemo-immunotherapy as first-line standard.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-keynote-966-lancet-2023","kind":"paper","name":"KEYNOTE-966: pembrolizumab plus gemcitabine and cisplatin for advanced biliary tract cancer","route":"/key-papers/paper-keynote-966-lancet-2023/","year":2023,"journal":"The Lancet","paperType":"rct","tldr":"Adding pembrolizumab to gemcitabine-cisplatin, with gemcitabine continued as maintenance, lengthened survival in advanced biliary tract cancer by about two months, confirming the role of chemo-immunotherapy shown by TOPAZ-1.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-krystal-1-crc-yaeger-nejm-2023","kind":"paper","name":"KRYSTAL-1: adagrasib with or without cetuximab in KRAS G12C-mutated colorectal cancer","route":"/key-papers/paper-krystal-1-crc-yaeger-nejm-2023/","year":2023,"journal":"New England Journal of Medicine","paperType":"observational","tldr":"The KRAS G12C inhibitor adagrasib on its own shrank about one in five previously treated colorectal cancers, but combined with the EGFR antibody cetuximab the response rate rose to nearly half, showing the two drugs are needed together in this disease.","via":[{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"}]},{"id":"paper-libretto-431-nejm-2023","kind":"paper","name":"LIBRETTO-431: first-line selpercatinib versus chemotherapy with or without pembrolizumab in RET fusion-positive lung cancer","route":"/key-papers/paper-libretto-431-nejm-2023/","year":2023,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Given as first treatment, selpercatinib more than doubled the time to progression compared with platinum-pemetrexed chemotherapy plus pembrolizumab in RET fusion-positive lung cancer, and protected against brain metastases.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-patil-low-dose-nivolumab-jco-2023","kind":"paper","name":"Low-dose immunotherapy in head and neck cancer: a randomised study (Tata Memorial)","route":"/key-papers/paper-patil-low-dose-nivolumab-jco-2023/","year":2023,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"Giving about one-twentieth of the standard dose of nivolumab alongside cheap oral chemotherapy nearly tripled one-year survival in advanced head and neck cancer, showing that immunotherapy can be made affordable without losing its effect.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-nrg-gy018-nejm-2023","kind":"paper","name":"NRG-GY018: pembrolizumab plus chemotherapy in advanced or recurrent endometrial cancer","route":"/key-papers/paper-nrg-gy018-nejm-2023/","year":2023,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding pembrolizumab to carboplatin-paclitaxel and continuing it as maintenance cut the risk of progression by 70 percent in mismatch repair-deficient endometrial cancer and by 46 percent in mismatch repair-proficient disease.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-jimenez-gaona-ivermectin-loja-ecuador-2023","kind":"paper","name":"Outcome of ivermectin in cancer treatment: an experience in Loja, Ecuador","route":"/key-papers/paper-jimenez-gaona-ivermectin-loja-ecuador-2023/","year":2023,"journal":"Nursing Reports","paperType":"observational","tldr":"A survey in rural Ecuador found that about one in five people with cancer were taking cattle ivermectin alongside their treatment, while the specialists interviewed said there was no evidence and did not recommend it.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]},{"id":"paper-heymach-aegean-perioperative-durvalumab-nejm-2023","kind":"paper","name":"Perioperative durvalumab for resectable non-small-cell lung cancer","route":"/key-papers/paper-heymach-aegean-perioperative-durvalumab-nejm-2023/","year":2023,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Giving immunotherapy both before and after lung cancer surgery cut the risk of recurrence by about a third, and left 17.2 percent of tumours with no viable cancer at all in the specimen.","via":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-provencio-nadim-ii-perioperative-nivolumab-stage-iii-nejm-2023","kind":"paper","name":"Perioperative nivolumab and chemotherapy in stage III non-small-cell lung cancer","route":"/key-papers/paper-provencio-nadim-ii-perioperative-nivolumab-stage-iii-nejm-2023/","year":2023,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"A Spanish trial of 86 patients with stage III lung cancer. Adding immunotherapy before surgery left 37 percent with no viable tumour in the specimen against 7 percent, and 85 percent were alive at two years against 64.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-foxtrot-preoperative-chemotherapy-colon-jco-2023","kind":"paper","name":"Preoperative chemotherapy for operable colon cancer: mature results of an international randomized controlled trial (FOxTROT)","route":"/key-papers/paper-foxtrot-preoperative-chemotherapy-colon-jco-2023/","year":2023,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"Six weeks of chemotherapy before the colon cancer operation, rather than all of it afterwards, shrank tumours, left fewer incomplete resections and cut two-year recurrence from 21.5 to 16.9 percent.","via":[{"id":"panitumumab","kind":"drug","name":"Panitumumab","route":"/drugs/panitumumab/"}]},{"id":"paper-turner-c-trak-tn-ctdna-pembrolizumab-ann-oncol-2023","kind":"paper","name":"Results of the c-TRAK TN trial: a clinical trial utilising ctDNA mutation tracking to detect molecular residual disease and trigger intervention in patients with moderate- and high-risk early-stage triple-negative breast cancer","route":"/key-papers/paper-turner-c-trak-tn-ctdna-pembrolizumab-ann-oncol-2023/","year":2023,"journal":"Annals of Oncology","paperType":"rct","tldr":"The UK trial that watched 161 women with early triple-negative breast cancer by three-monthly blood tests for tumour DNA: 27 percent tested positive within a year, but by then nearly three quarters already had visible metastases, and none of the five who started pembrolizumab cleared the DNA. The lesson was to test earlier and more sensitively.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-rojas-mrna-neoantigen-vaccine-pancreatic-nature-2023","kind":"paper","name":"Rojas 2023: a personalised mRNA vaccine trained T cells against each patient's pancreatic cancer, and those who responded stayed cancer-free longer","route":"/key-papers/paper-rojas-mrna-neoantigen-vaccine-pancreatic-nature-2023/","year":2023,"journal":"Nature","paperType":"translational","tldr":"Individualised mRNA vaccines encoding up to 20 of each patient's tumour mutations generated strong T-cell responses in half of pancreatic cancer patients after surgery, and those responders had far fewer relapses.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"}]},{"id":"paper-rosewood-zanubrutinib-obinutuzumab-follicular-jco-2023","kind":"paper","name":"ROSEWOOD: a phase II randomized study of zanubrutinib plus obinutuzumab versus obinutuzumab monotherapy in patients with relapsed or refractory follicular lymphoma","route":"/key-papers/paper-rosewood-zanubrutinib-obinutuzumab-follicular-jco-2023/","year":2023,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"Adding a targeted tablet to an antibody roughly halved the risk of progression in follicular lymphoma that had already returned twice.","via":[{"id":"obinutuzumab","kind":"drug","name":"Obinutuzumab","route":"/drugs/obinutuzumab/"}]},{"id":"paper-ruby-nejm-2023","kind":"paper","name":"RUBY: dostarlimab with chemotherapy for advanced or recurrent endometrial cancer","route":"/key-papers/paper-ruby-nejm-2023/","year":2023,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding the PD-1 antibody dostarlimab to first-line chemotherapy for advanced endometrial cancer cut progression by 72% in tumours with defective mismatch repair and by about a third overall, and later improved survival.","via":[{"id":"dostarlimab","kind":"drug","name":"Dostarlimab","route":"/drugs/dostarlimab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-xu-jama","kind":"paper","name":"Sintilimab Plus Chemotherapy for Unresectable Gastric or Gastroesophageal Junction Cancer: The ORIENT-16 Randomized Clinical Trial","route":"/key-papers/paper-xu-jama/","year":2023,"journal":"JAMA","paperType":"rct","tldr":"Paper cited by one trial page and one treatment page, indexed on Europe PMC as PubMed record 38051328 and published in JAMA; the citing pages link this DOI, which is how the record was matched.","via":[{"id":"sintilimab","kind":"drug","name":"Sintilimab","route":"/drugs/sintilimab/"}]},{"id":"paper-spotlight-lancet-2023","kind":"paper","name":"SPOTLIGHT: zolbetuximab, the first Claudin 18.2 antibody, added to chemotherapy in gastric cancer","route":"/key-papers/paper-spotlight-lancet-2023/","year":2023,"journal":"The Lancet","paperType":"rct","tldr":"In stomach cancers that express the protein Claudin 18.2, adding the antibody zolbetuximab to chemotherapy extended survival by nearly three months, making Claudin 18.2 a new biomarker to test for.","via":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"paper-prager-sunlight-trifluridine-tipiracil-bevacizumab-nejm-2023","kind":"paper","name":"Trifluridine-tipiracil and bevacizumab in refractory metastatic colorectal cancer (SUNLIGHT)","route":"/key-papers/paper-prager-sunlight-trifluridine-tipiracil-bevacizumab-nejm-2023/","year":2023,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding a cheap old antibody to the refractory-line tablet took median survival from 7.5 to 10.8 months, the largest gain in this setting since the setting existed.","via":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"}]},{"id":"paper-strickler-mountaineer-tucatinib-trastuzumab-lancet-oncol-2023","kind":"paper","name":"Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER)","route":"/key-papers/paper-strickler-mountaineer-tucatinib-trastuzumab-lancet-oncol-2023/","year":2023,"journal":"The Lancet Oncology","paperType":"rct","tldr":"A HER2 pill with an antibody gave a 38 percent response rate in chemotherapy-refractory HER2-positive bowel cancer, and became the first HER2-directed regimen approved for the disease.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"paper-ricciuti-tmb-pd-l1-levels-jama-oncol-2022","kind":"paper","name":"Association of high tumor mutation burden in non-small cell lung cancers with increased immune infiltration and improved clinical outcomes of PD-L1 blockade across PD-L1 expression levels","route":"/key-papers/paper-ricciuti-tmb-pd-l1-levels-jama-oncol-2022/","year":2022,"journal":"JAMA Oncology","paperType":"observational","tldr":"Pooling more than fifteen hundred patients showed that the more mutations a lung cancer carries the better immunotherapy works, at every level of the PD-L1 stain, but the best dividing line was about twice the number the licensing authorities use.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-cercek-dostarlimab-rectal-nejm-2022","kind":"paper","name":"Cercek 2022: six months of dostarlimab alone made rectal cancer disappear in every patient with mismatch-repair deficiency","route":"/key-papers/paper-cercek-dostarlimab-rectal-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"translational","tldr":"All 12 patients with locally advanced dMMR rectal cancer had a complete clinical response to a PD-1 antibody alone, avoiding chemotherapy, radiotherapy and surgery.","via":[{"id":"dostarlimab","kind":"drug","name":"Dostarlimab","route":"/drugs/dostarlimab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-hoang-ivermectin-toxicity-clin-toxicol-2022","kind":"paper","name":"Characteristics of ivermectin toxicity in patients taking veterinary and human formulations for the prevention and treatment of COVID-19","route":"/key-papers/paper-hoang-ivermectin-toxicity-clin-toxicol-2022/","year":2022,"journal":"Clinical Toxicology","paperType":"observational","tldr":"An Oregon poison centre saw 37 people poisoned by ivermectin in six months of the pandemic; 30 had nervous-system effects, 21 were admitted to hospital and one died, with veterinary products giving the largest doses and the most confusion.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]},{"id":"paper-checkmate-648-nejm-2022","kind":"paper","name":"CheckMate 648: nivolumab combination therapy in advanced oesophageal squamous cell carcinoma","route":"/key-papers/paper-checkmate-648-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding nivolumab to chemotherapy, or combining nivolumab with ipilimumab without chemotherapy, lengthened survival compared with chemotherapy alone in advanced oesophageal squamous cell carcinoma, with the largest gains in PD-L1-positive tumours.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"id":"paper-checkmate-816-nejm-2022","kind":"paper","name":"CheckMate 816: three cycles of nivolumab plus chemotherapy before lung cancer surgery","route":"/key-papers/paper-checkmate-816-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Just three cycles of chemotherapy with the immunotherapy nivolumab before surgery wiped out all viable tumour in a quarter of patients and reduced relapse or death by about a third, without making surgery harder.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-destiny-lung01-nejm-2022","kind":"paper","name":"DESTINY-Lung01: trastuzumab deruxtecan in HER2-mutant non-small-cell lung cancer","route":"/key-papers/paper-destiny-lung01-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"observational","tldr":"Trastuzumab deruxtecan shrank tumours in more than half of patients with previously treated HER2-mutant lung cancer, a driver with no approved therapy until this study, though lung inflammation was a serious side effect.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-ricciuti-stk11-keap1-kras-immunotherapy-jto-2022","kind":"paper","name":"Diminished efficacy of programmed death-(ligand)1 inhibition in STK11- and KEAP1-mutant lung adenocarcinoma is affected by KRAS mutation status","route":"/key-papers/paper-ricciuti-stk11-keap1-kras-immunotherapy-jto-2022/","year":2022,"journal":"Journal of Thoracic Oncology","paperType":"observational","tldr":"Two genes long blamed for immunotherapy failure in lung cancer turn out to matter only when the tumour also has a mutated KRAS gene. In tumours without it, the same mutations made no difference at all.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-empower-cervical-1-cemiplimab-nejm-2022","kind":"paper","name":"EMPOWER-Cervical 1: cemiplimab versus chemotherapy in recurrent cervical cancer after platinum","route":"/key-papers/paper-empower-cervical-1-cemiplimab-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"The PD-1 antibody cemiplimab lengthened survival compared with single-agent chemotherapy in recurrent cervical cancer after platinum, regardless of PD-L1 expression, the first immunotherapy to show a survival benefit in this disease.","via":[{"id":"cemiplimab","kind":"drug","name":"Cemiplimab","route":"/drugs/cemiplimab/"}]},{"id":"paper-spigel-pacific-five-year-survival-jco-2022","kind":"paper","name":"Five-year survival outcomes from the PACIFIC trial: durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer","route":"/key-papers/paper-spigel-pacific-five-year-survival-jco-2022/","year":2022,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"Five years after the PACIFIC trial, 42.9 percent of patients given a year of immunotherapy after chemoradiotherapy were still alive, against 33.4 percent of those given placebo. A third of them had never relapsed.","via":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-himalaya-nejm-evidence-2022","kind":"paper","name":"HIMALAYA: tremelimumab plus durvalumab in unresectable hepatocellular carcinoma","route":"/key-papers/paper-himalaya-nejm-evidence-2022/","year":2022,"journal":"NEJM Evidence","paperType":"rct","tldr":"A single priming dose of the CTLA-4 antibody tremelimumab followed by durvalumab lengthened survival compared with sorafenib in advanced liver cancer without the bleeding risk of bevacizumab, giving a second first-line immunotherapy standard.","via":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"},{"id":"tremelimumab","kind":"drug","name":"Tremelimumab","route":"/drugs/tremelimumab/"}]},{"id":"paper-shine-ibrutinib-bendamustine-rituximab-mantle-cell-nejm-2022","kind":"paper","name":"Ibrutinib plus bendamustine and rituximab in untreated mantle-cell lymphoma","route":"/key-papers/paper-shine-ibrutinib-bendamustine-rituximab-mantle-cell-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding a targeted tablet to first-line chemotherapy gave older people with mantle cell lymphoma about two and a half more years before relapse, without helping them live longer.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"paper-keynote-355-nejm-2022","kind":"paper","name":"KEYNOTE-355: pembrolizumab plus chemotherapy for PD-L1-positive advanced triple-negative breast cancer","route":"/key-papers/paper-keynote-355-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding pembrolizumab to first-line chemotherapy lengthened survival by almost seven months in advanced triple-negative breast cancer whose tumours had a PD-L1 combined positive score of 10 or more.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-keynote-522-nejm-2022","kind":"paper","name":"KEYNOTE-522: adding pembrolizumab before and after surgery in early triple-negative breast cancer","route":"/key-papers/paper-keynote-522-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding the immunotherapy pembrolizumab to chemotherapy before surgery, then continuing it afterwards, cut the risk of relapse or death by about a third in stage II-III triple-negative breast cancer and later improved survival.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-keynote-716-lancet-2022","kind":"paper","name":"KEYNOTE-716: adjuvant pembrolizumab versus placebo in completely resected stage IIB or IIC melanoma","route":"/key-papers/paper-keynote-716-lancet-2022/","year":2022,"journal":"The Lancet","paperType":"rct","tldr":"A year of pembrolizumab after surgery for stage IIB or IIC melanoma reduced recurrences and distant metastases by about 35 to 40 percent, extending adjuvant immunotherapy to node-negative but thick or ulcerated melanomas.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-keynote-775-nejm-2022","kind":"paper","name":"KEYNOTE-775: lenvatinib plus pembrolizumab versus chemotherapy for previously treated advanced endometrial cancer","route":"/key-papers/paper-keynote-775-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"After platinum chemotherapy, the combination of the kinase inhibitor lenvatinib and pembrolizumab lengthened survival compared with doxorubicin or paclitaxel in advanced endometrial cancer, including in the mismatch repair-proficient majority.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-gross-neoadjuvant-cemiplimab-cscc-nejm-2022","kind":"paper","name":"Neoadjuvant cemiplimab for stage II to IV cutaneous squamous cell carcinoma","route":"/key-papers/paper-gross-neoadjuvant-cemiplimab-cscc-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"observational","tldr":"Giving four doses of cemiplimab before surgery for resectable cutaneous squamous cell carcinoma eliminated all viable tumour in half of patients and left only minimal residual disease in another 13 percent, opening the way to smaller operations and less radiotherapy.","via":[{"id":"cemiplimab","kind":"drug","name":"Cemiplimab","route":"/drugs/cemiplimab/"}]},{"id":"paper-polarix-polatuzumab-rchp-nejm-2022","kind":"paper","name":"POLARIX: swapping vincristine for the antibody-drug conjugate polatuzumab vedotin in first-line treatment of diffuse large B-cell lymphoma","route":"/key-papers/paper-polarix-polatuzumab-rchp-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Replacing one chemotherapy drug in R-CHOP with a CD79b antibody-drug conjugate modestly reduced progression (2-year PFS 76.7% versus 70.2%) without changing survival or side effects.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"paper-relativity-047-nejm-2022","kind":"paper","name":"RELATIVITY-047: relatlimab plus nivolumab, the first LAG-3 checkpoint combination, in untreated advanced melanoma","route":"/key-papers/paper-relativity-047-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding an antibody against a second immune brake, LAG-3, to nivolumab delayed progression in advanced melanoma compared with nivolumab alone, with far fewer serious side effects than the ipilimumab combination.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"relatlimab-nivolumab","kind":"drug","name":"Relatlimab + nivolumab","route":"/drugs/relatlimab-nivolumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-rohaas-til-vs-ipilimumab-nejm-2022","kind":"paper","name":"Rohaas 2022: the first randomised trial of TIL therapy, against ipilimumab, in advanced melanoma","route":"/key-papers/paper-rohaas-til-vs-ipilimumab-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"In a head-to-head trial, tumour-infiltrating lymphocyte therapy halved the risk of progression compared with ipilimumab in melanoma that had mostly already failed PD-1 blockade.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"}]},{"id":"paper-ishiguro-dichloroacetate-ivermectin-cureus-2022","kind":"paper","name":"Synergistic anti-tumor effect of dichloroacetate and ivermectin","route":"/key-papers/paper-ishiguro-dichloroacetate-ivermectin-cureus-2022/","year":2022,"journal":"Cureus","paperType":"observational","tldr":"Three patients treated at a private clinic with dichloroacetate, omeprazole, tamoxifen and ivermectin were reported to have relief of symptoms; there was no control, no measured tumour response and no follow-up study.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]},{"id":"paper-topaz-1-nejm-evidence-2022","kind":"paper","name":"TOPAZ-1: durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer","route":"/key-papers/paper-topaz-1-nejm-evidence-2022/","year":2022,"journal":"NEJM Evidence","paperType":"rct","tldr":"Adding durvalumab to gemcitabine-cisplatin lengthened survival in advanced bile duct and gallbladder cancer, the first improvement on chemotherapy alone in more than a decade, with about a quarter of patients alive at two years.","via":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"}]},{"id":"paper-tuxedo-1-trastuzumab-deruxtecan-brain-metastases-nat-med-2022","kind":"paper","name":"TUXEDO-1: trastuzumab deruxtecan in HER2-positive breast cancer with active brain metastases","route":"/key-papers/paper-tuxedo-1-trastuzumab-deruxtecan-brain-metastases-nat-med-2022/","year":2022,"journal":"Nature Medicine","paperType":"observational","tldr":"In a small trial, the antibody-drug conjugate trastuzumab deruxtecan shrank brain metastases in almost three quarters of women with HER2-positive breast cancer, showing that a large antibody-based drug can work inside the brain.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-asco-pembrolizumab-early-tnbc-rapid-update-jco-2022","kind":"paper","name":"Use of Immune Checkpoint Inhibitor Pembrolizumab in the Treatment of High-Risk, Early-Stage Triple-Negative Breast Cancer: ASCO Guideline Rapid Recommendation Update","route":"/key-papers/paper-asco-pembrolizumab-early-tnbc-rapid-update-jco-2022/","year":2022,"journal":"Journal of Clinical Oncology","paperType":"guideline","tldr":"The 2022 fast-track amendment in which the US oncology society added pembrolizumab before and after surgery for high-risk early triple-negative breast cancer, a year after its main guideline had said the evidence was insufficient.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-felip-impower010-adjuvant-atezolizumab-lancet-2021","kind":"paper","name":"Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010)","route":"/key-papers/paper-felip-impower010-adjuvant-atezolizumab-lancet-2021/","year":2021,"journal":"The Lancet","paperType":"rct","tldr":"The first trial to show that immunotherapy after lung cancer surgery delays recurrence. The benefit was concentrated in patients whose tumours expressed PD-L1.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-asco-irae-guideline-jco-2021","kind":"paper","name":"ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors","route":"/key-papers/paper-asco-irae-guideline-jco-2021/","year":2021,"journal":"Journal of Clinical Oncology","paperType":"guideline","tldr":"The ASCO 2021 guideline is the consensus rulebook for checkpoint-inhibitor toxicity: grade the problem, hold or stop the drug, give steroids early, escalate to other immunosuppressants if they fail, and involve specialists.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-raghav-atezolizumab-bevacizumab-peritoneal-mesothelioma-cancer-discov-2021","kind":"paper","name":"Atezolizumab plus bevacizumab in advanced malignant peritoneal mesothelioma","route":"/key-papers/paper-raghav-atezolizumab-bevacizumab-peritoneal-mesothelioma-cancer-discov-2021/","year":2021,"journal":"Cancer Discovery","paperType":"observational","tldr":"In a small trial combining PD-L1 and VEGF blockade, four in ten patients with previously treated peritoneal mesothelioma responded, with responses lasting well over a year, the first dedicated prospective evidence for immunotherapy in this rare disease.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"}]},{"id":"paper-ux023t-cl201-jan-de-beur-jbmr-2021","kind":"paper","name":"Burosumab for the treatment of tumor-induced osteomalacia (UX023T-CL201)","route":"/key-papers/paper-ux023t-cl201-jan-de-beur-jbmr-2021/","year":2021,"journal":"Journal of Bone and Mineral Research","paperType":"observational","tldr":"In 14 adults whose bones had softened because a hidden tumour was making them lose phosphate, blocking the hormone responsible brought blood phosphate back to normal for nearly three years and let a third of their fractures heal fully.","via":[{"id":"burosumab","kind":"drug","name":"Burosumab","route":"/drugs/burosumab/"}]},{"id":"paper-captain-1st-camrelizumab-chemotherapy-npc-lancet-oncol-2021","kind":"paper","name":"CAPTAIN-1st: camrelizumab versus placebo with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma","route":"/key-papers/paper-captain-1st-camrelizumab-chemotherapy-npc-lancet-oncol-2021/","year":2021,"journal":"The Lancet Oncology","paperType":"rct","tldr":"A second PD-1 antibody, camrelizumab, also lengthened progression-free survival when added to gemcitabine and cisplatin in metastatic nasopharyngeal cancer, confirming that chemo-immunotherapy is the new first-line standard.","via":[{"id":"camrelizumab","kind":"drug","name":"Camrelizumab","route":"/drugs/camrelizumab/"}]},{"id":"paper-cemiplimab-bcc-stratigos-lancet-oncol-2021","kind":"paper","name":"Cemiplimab in locally advanced basal cell carcinoma after hedgehog inhibitor therapy","route":"/key-papers/paper-cemiplimab-bcc-stratigos-lancet-oncol-2021/","year":2021,"journal":"The Lancet Oncology","paperType":"observational","tldr":"In patients whose locally advanced basal cell carcinoma had progressed on or could not tolerate a hedgehog inhibitor, cemiplimab shrank tumours in about three in ten, giving a second-line option where none existed.","via":[{"id":"cemiplimab","kind":"drug","name":"Cemiplimab","route":"/drugs/cemiplimab/"}]},{"id":"paper-checkmate-577-nejm-2021","kind":"paper","name":"CheckMate 577: adjuvant nivolumab in resected oesophageal or gastro-oesophageal junction cancer","route":"/key-papers/paper-checkmate-577-nejm-2021/","year":2021,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"A year of nivolumab after chemoradiotherapy and surgery doubled disease-free survival in patients with oesophageal or junctional cancer who still had residual tumour at surgery, the first adjuvant therapy to work in this setting.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"id":"paper-checkmate-649-lancet-2021","kind":"paper","name":"CheckMate 649: nivolumab plus chemotherapy as first treatment for advanced gastric, gastro-oesophageal junction and oesophageal adenocarcinoma","route":"/key-papers/paper-checkmate-649-lancet-2021/","year":2021,"journal":"The Lancet","paperType":"rct","tldr":"Adding the immunotherapy nivolumab to first-line chemotherapy helped patients with advanced stomach and oesophageal adenocarcinoma live longer, especially when the tumour showed PD-L1, making chemo-immunotherapy the new standard.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-checkmate-743-lancet-2021","kind":"paper","name":"CheckMate 743: first-line nivolumab plus ipilimumab in unresectable pleural mesothelioma","route":"/key-papers/paper-checkmate-743-lancet-2021/","year":2021,"journal":"The Lancet","paperType":"rct","tldr":"Dual immunotherapy with nivolumab and ipilimumab lengthened survival compared with platinum-pemetrexed chemotherapy in pleural mesothelioma, the first improvement in first-line treatment in almost twenty years, with the largest gain in non-epithelioid tumours.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"id":"paper-nakamura-triumph-ctdna-pertuzumab-trastuzumab-her2-colorectal-nat-med-2021","kind":"paper","name":"Circulating tumor DNA-guided treatment with pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer: a phase 2 trial (TRIUMPH)","route":"/key-papers/paper-nakamura-triumph-ctdna-pertuzumab-trastuzumab-her2-colorectal-nat-med-2021/","year":2021,"journal":"Nature Medicine","paperType":"rct","tldr":"The first trial to let a blood test decide who joins: patients whose plasma showed extra HER2 responded to dual HER2 antibodies just as often as those selected on tissue, while a matched group on 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breast cancer (with 2026 expression of concern)","route":"/key-papers/paper-draganov-ivermectin-cold-tumours-npj-breast-cancer-2021/","year":2021,"journal":"npj Breast Cancer","paperType":"basic","tldr":"The mouse study behind the current trials: ivermectin on its own did nothing to breast tumours in mice, but with an anti-PD-1 antibody the pair shrank them. The journal has since flagged duplicated images in one figure and the raw data are gone.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-tang-ivermectin-potential-anticancer-pharmacol-res-2021","kind":"paper","name":"Ivermectin, a potential anticancer drug derived from an antiparasitic drug","route":"/key-papers/paper-tang-ivermectin-potential-anticancer-pharmacol-res-2021/","year":2021,"journal":"Pharmacological Research","paperType":"review","tldr":"A 2021 review of the pathways through which ivermectin killed cancer cells in the laboratory, written as a case for testing it in people.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]},{"id":"paper-jupiter-02-toripalimab-chemotherapy-npc-nat-med-2021","kind":"paper","name":"JUPITER-02: toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma","route":"/key-papers/paper-jupiter-02-toripalimab-chemotherapy-npc-nat-med-2021/","year":2021,"journal":"Nature Medicine","paperType":"rct","tldr":"Adding the PD-1 antibody toripalimab to gemcitabine and cisplatin lengthened the time before metastatic nasopharyngeal cancer progressed by about four months, and later improved survival, making chemo-immunotherapy the first-line standard.","via":[{"id":"toripalimab","kind":"drug","name":"Toripalimab","route":"/drugs/toripalimab/"}]},{"id":"paper-keynote-057-lancet-oncol-2021","kind":"paper","name":"KEYNOTE-057: pembrolizumab for BCG-unresponsive non-muscle-invasive bladder cancer with carcinoma in situ","route":"/key-papers/paper-keynote-057-lancet-oncol-2021/","year":2021,"journal":"The Lancet Oncology","paperType":"observational","tldr":"In patients whose high-risk bladder cancer no longer responded to BCG and who could not or would not have their bladder removed, pembrolizumab cleared the disease in about four in ten, with a response lasting a year or more in roughly half of those.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-keynote-204-pembrolizumab-vs-brentuximab-rr-hodgkin-lancet-oncol-2021","kind":"paper","name":"KEYNOTE-204: pembrolizumab versus brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma","route":"/key-papers/paper-keynote-204-pembrolizumab-vs-brentuximab-rr-hodgkin-lancet-oncol-2021/","year":2021,"journal":"The Lancet Oncology","paperType":"rct","tldr":"In a head-to-head trial, the PD-1 antibody pembrolizumab kept relapsed Hodgkin lymphoma at bay for longer than brentuximab vedotin, making immunotherapy the preferred choice after transplant failure or for patients who cannot have a transplant.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-keynote-564-nejm-2021","kind":"paper","name":"KEYNOTE-564: a year of pembrolizumab after kidney cancer surgery","route":"/key-papers/paper-keynote-564-nejm-2021/","year":2021,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"One year of pembrolizumab after surgery for high-risk kidney cancer reduced relapses by about a third and, in later follow-up, became the first adjuvant treatment to help kidney cancer patients live longer.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-keynote-590-lancet-2021","kind":"paper","name":"KEYNOTE-590: pembrolizumab plus chemotherapy for first-line treatment of advanced oesophageal cancer","route":"/key-papers/paper-keynote-590-lancet-2021/","year":2021,"journal":"The Lancet","paperType":"rct","tldr":"Adding pembrolizumab to cisplatin-fluorouracil lengthened survival in advanced oesophageal cancer of both histologies, most clearly in squamous cell carcinoma and in tumours with high PD-L1, establishing chemo-immunotherapy as the first-line standard.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-keynote-826-nejm-2021","kind":"paper","name":"KEYNOTE-826: pembrolizumab plus chemotherapy with or without bevacizumab for persistent, recurrent or metastatic cervical cancer","route":"/key-papers/paper-keynote-826-nejm-2021/","year":2021,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding pembrolizumab to first-line chemotherapy, with or without bevacizumab, lengthened survival in advanced cervical cancer, the first improvement in the disease since bevacizumab was added seven years earlier.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-tjulandin-prolgolimab-miraculum-ejc-2021","kind":"paper","name":"MIRACULUM: prolgolimab, the first Russian-developed anti-PD-1 antibody, in advanced melanoma","route":"/key-papers/paper-tjulandin-prolgolimab-miraculum-ejc-2021/","year":2021,"journal":"European Journal of Cancer","paperType":"rct","tldr":"The trial behind Russia's own PD-1 antibody: 126 patients with advanced melanoma, an objective response in 38 per cent on the fortnightly dose and 29 per cent on the three-weekly dose, and severe treatment-related side effects in 13 and 3 per cent.","via":[{"id":"bcd-100","kind":"drug","name":"BCD-100","route":"/drugs/bcd-100/"}]},{"id":"paper-gay-sclc-subtypes-inflamed-cancer-cell-2021","kind":"paper","name":"Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities","route":"/key-papers/paper-gay-sclc-subtypes-inflamed-cancer-cell-2021/","year":2021,"journal":"Cancer Cell","paperType":"translational","tldr":"Reanalysing gene activity in small-cell lung cancer tumours found that the fourth kind is not defined by a control protein at all but by inflammation, and it is the one kind that clearly gains from adding immunotherapy.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-rugo-pd-l1-assay-comparison-impassion130-jnci-2021","kind":"paper","name":"PD-L1 Immunohistochemistry Assay Comparison in Atezolizumab Plus nab-Paclitaxel-Treated Advanced Triple-Negative Breast Cancer","route":"/key-papers/paper-rugo-pd-l1-assay-comparison-impassion130-jnci-2021/","year":2021,"journal":"Journal of the National Cancer Institute","paperType":"translational","tldr":"Three different PD-L1 tests run on the same 614 IMpassion130 tumours called 46, 75 and 73 percent of them positive and agreed with each other only about 69 percent of the time; the benefit of atezolizumab was concentrated in the tumours all three called positive.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-javle-mypathway-her2-biliary-lancet-oncol-2021","kind":"paper","name":"Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): a multicentre, open-label, phase 2a, multiple basket study","route":"/key-papers/paper-javle-mypathway-her2-biliary-lancet-oncol-2021/","year":2021,"journal":"The Lancet Oncology","paperType":"observational","tldr":"Two HER2 antibodies together shrank tumours in about a quarter of 39 patients with HER2-positive bile duct or gallbladder cancer that had already been treated, with manageable side 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more treatments, including tumours that had progressed on other HER2 drugs.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-zebra-pembrolizumab-small-bowel-adenocarcinoma-ccr-2021","kind":"paper","name":"ZEBRA: pembrolizumab in advanced small bowel adenocarcinoma","route":"/key-papers/paper-zebra-pembrolizumab-small-bowel-adenocarcinoma-ccr-2021/","year":2021,"journal":"Clinical Cancer Research","paperType":"observational","tldr":"Immunotherapy on its own helped only a few patients with advanced small bowel adenocarcinoma, mainly those whose tumours had mismatch repair deficiency, so the drug is reserved for that group.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-anbl1221-expansion-dinutuximab-gm-csf-mody-jco-2020","kind":"paper","name":"ANBL1221 expansion: irinotecan, temozolomide and dinutuximab with GM-CSF in refractory or relapsed neuroblastoma","route":"/key-papers/paper-anbl1221-expansion-dinutuximab-gm-csf-mody-jco-2020/","year":2020,"journal":"Journal of Clinical Oncology","paperType":"observational","tldr":"Across 53 children treated with irinotecan, temozolomide and dinutuximab for relapsed neuroblastoma, four in ten had their tumours shrink and 85 percent were alive a year later, confirming the combination as the standard salvage treatment.","via":[{"id":"dinutuximab","kind":"drug","name":"Dinutuximab (ch14.18) / dinutuximab beta","route":"/drugs/dinutuximab/"}]},{"id":"paper-herbst-impower110-atezolizumab-pd-l1-nejm-2020","kind":"paper","name":"Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC","route":"/key-papers/paper-herbst-impower110-atezolizumab-pd-l1-nejm-2020/","year":2020,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"In the patients whose tumours showed the most PD-L1, immunotherapy alone gave a median survival of 20.2 months against 13.1 on chemotherapy, with far fewer severe side effects.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-destiny-gastric01-nejm-2020","kind":"paper","name":"DESTINY-Gastric01: trastuzumab deruxtecan in previously treated HER2-positive gastric cancer","route":"/key-papers/paper-destiny-gastric01-nejm-2020/","year":2020,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Trastuzumab deruxtecan shrank tumours in half of patients with HER2-positive gastric cancer that had progressed after trastuzumab, compared with 14 percent on chemotherapy, and lengthened survival by over four months.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-elevate-tn-acalabrutinib-lancet-2020","kind":"paper","name":"ELEVATE-TN: acalabrutinib, alone or with obinutuzumab, against chemo-immunotherapy in untreated CLL","route":"/key-papers/paper-elevate-tn-acalabrutinib-lancet-2020/","year":2020,"journal":"The Lancet","paperType":"rct","tldr":"In ELEVATE-TN, acalabrutinib, a second-generation BTK inhibitor, with or without an antibody, cut the risk of progression by 80-90% compared with chlorambucil-obinutuzumab in older or unfit patients with CLL.","via":[{"id":"obinutuzumab","kind":"drug","name":"Obinutuzumab","route":"/drugs/obinutuzumab/"}]},{"id":"paper-garnet-dostarlimab-oaknin-jama-oncol-2020","kind":"paper","name":"GARNET: dostarlimab in mismatch repair-deficient recurrent or advanced endometrial cancer","route":"/key-papers/paper-garnet-dostarlimab-oaknin-jama-oncol-2020/","year":2020,"journal":"JAMA Oncology","paperType":"observational","tldr":"The PD-1 antibody dostarlimab shrank tumours in about four in ten women with mismatch repair-deficient endometrial cancer that had progressed after platinum chemotherapy, with most responses still ongoing after a year.","via":[{"id":"dostarlimab","kind":"drug","name":"Dostarlimab","route":"/drugs/dostarlimab/"}]},{"id":"paper-her2climb-brain-lin-jco-2020","kind":"paper","name":"HER2CLIMB brain metastases analysis: intracranial efficacy and survival with tucatinib","route":"/key-papers/paper-her2climb-brain-lin-jco-2020/","year":2020,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"Among the HER2CLIMB patients with brain metastases, tucatinib doubled the intracranial response rate, cut the risk of intracranial progression or death by about two thirds and lengthened survival.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-her2climb-nejm-2020","kind":"paper","name":"HER2CLIMB: tucatinib with trastuzumab and capecitabine for HER2-positive metastatic breast cancer, including brain metastases","route":"/key-papers/paper-her2climb-nejm-2020/","year":2020,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding the brain-penetrant HER2 pill tucatinib to trastuzumab and capecitabine lengthened survival in heavily pretreated HER2-positive metastatic breast cancer, and uniquely the trial included patients with active brain metastases, who also benefited.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-imbrave150-nejm-2020","kind":"paper","name":"IMbrave150: atezolizumab plus bevacizumab replaces sorafenib as first treatment for advanced liver 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Journal of Medicine","paperType":"rct","tldr":"Continuing with the immunotherapy avelumab after chemotherapy had controlled advanced bladder cancer lengthened survival by about seven months compared with watching and waiting.","via":[{"id":"avelumab","kind":"drug","name":"Avelumab","route":"/drugs/avelumab/"}]},{"id":"paper-keynote-062-shitara-jama-oncol-2020","kind":"paper","name":"KEYNOTE-062: pembrolizumab or pembrolizumab plus chemotherapy versus chemotherapy in PD-L1-positive advanced gastric cancer","route":"/key-papers/paper-keynote-062-shitara-jama-oncol-2020/","year":2020,"journal":"JAMA Oncology","paperType":"rct","tldr":"In first-line PD-L1-positive gastric cancer, pembrolizumab alone was no worse than chemotherapy for survival but did not beat it, and adding it to chemotherapy did not help either; the exception was microsatellite-unstable tumours, which did dramatically better with pembrolizumab.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-keynote-158-pembrolizumab-msi-high-noncolorectal-jco-2020","kind":"paper","name":"KEYNOTE-158: pembrolizumab in non-colorectal high microsatellite instability or mismatch repair-deficient cancer","route":"/key-papers/paper-keynote-158-pembrolizumab-msi-high-noncolorectal-jco-2020/","year":2020,"journal":"Journal of Clinical Oncology","paperType":"observational","tldr":"Pembrolizumab shrank tumours in about a third of patients with mismatch repair-deficient cancers of many different organs, with responses that often lasted years; the pancreatic cancer group responded less often than most. It is the trial behind the tissue-agnostic approval for MSI-high cancer.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-keynote-177-nejm-2020","kind":"paper","name":"KEYNOTE-177: pembrolizumab instead of chemotherapy as first treatment for mismatch-repair-deficient metastatic colorectal cancer","route":"/key-papers/paper-keynote-177-nejm-2020/","year":2020,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"For the roughly 5% of metastatic bowel cancers with defective DNA mismatch repair, pembrolizumab alone lengthened the time without progression compared with chemotherapy, with far fewer severe side effects, and 83% of responses lasted two years or more. It made first-line pembrolizumab the standard for this group.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-antonarakis-keynote-199-pembrolizumab-jco-2020","kind":"paper","name":"KEYNOTE-199: pembrolizumab for treatment-refractory metastatic castration-resistant prostate cancer","route":"/key-papers/paper-antonarakis-keynote-199-pembrolizumab-jco-2020/","year":2020,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"Checkpoint immunotherapy transformed several cancers and did almost nothing here. In 258 men with advanced prostate cancer, about 1 in 20 had a response, and whether the tumour expressed PD-L1 made no difference.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-keynote-629-pembrolizumab-cscc-grob-jco-2020","kind":"paper","name":"KEYNOTE-629: pembrolizumab monotherapy for recurrent or metastatic cutaneous squamous cell carcinoma","route":"/key-papers/paper-keynote-629-pembrolizumab-cscc-grob-jco-2020/","year":2020,"journal":"Journal of Clinical Oncology","paperType":"observational","tldr":"Pembrolizumab shrank tumours in about a third of patients with recurrent or metastatic cutaneous squamous cell carcinoma, with most responses lasting beyond a year, leading to its approval as an alternative to cemiplimab.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-asco-metastatic-pancreatic-cancer-guideline-update-jco-2020","kind":"paper","name":"Metastatic Pancreatic Cancer: ASCO Guideline Update","route":"/key-papers/paper-asco-metastatic-pancreatic-cancer-guideline-update-jco-2020/","year":2020,"journal":"Journal of Clinical Oncology","paperType":"guideline","tldr":"The 2020 American guideline update that told doctors to test every treatment-eligible patient with metastatic pancreatic cancer for inherited BRCA changes, mismatch repair deficiency and TRK fusions, because each now had a drug attached.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-schoenfeld-smarca4-alterations-lung-ccr-2020","kind":"paper","name":"The genomic landscape of SMARCA4 alterations and associations with outcomes in patients with lung cancer","route":"/key-papers/paper-schoenfeld-smarca4-alterations-lung-ccr-2020/","year":2020,"journal":"Clinical Cancer Research","paperType":"observational","tldr":"One of the most commonly mutated genes in lung cancer turns out to come in two kinds: one that destroys the protein and carries the worst prognosis, and one that leaves it intact. Both do worse than average, and both do better than average on immunotherapy.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-trophimmun-avelumab-chemoresistant-gtn-you-jco-2020","kind":"paper","name":"TROPHIMMUN cohort A: avelumab in gestational trophoblastic tumours resistant to single-agent chemotherapy","route":"/key-papers/paper-trophimmun-avelumab-chemoresistant-gtn-you-jco-2020/","year":2020,"journal":"Journal of Clinical Oncology","paperType":"observational","tldr":"The PD-L1 antibody avelumab cured about half of women whose gestational trophoblastic tumour had stopped responding to single-drug chemotherapy, with mild side effects.","via":[{"id":"avelumab","kind":"drug","name":"Avelumab","route":"/drugs/avelumab/"}]},{"id":"paper-barroso-sousa-tmb-pten-ici-mtnbc-ccr-2020","kind":"paper","name":"Tumor mutational burden and PTEN alterations as molecular correlates of response to PD-1/L1 blockade in metastatic triple-negative breast cancer","route":"/key-papers/paper-barroso-sousa-tmb-pten-ici-mtnbc-ccr-2020/","year":2020,"journal":"Clinical Cancer Research","paperType":"observational","tldr":"In 62 women with metastatic triple-negative cancer treated with immunotherapy, high mutation burden (18%) went with a year of progression-free time versus under four months, while PTEN loss (29%) went with almost no responses.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-eng-imblaze370-atezolizumab-cobimetinib-colorectal-lancet-oncol-2019","kind":"paper","name":"Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370)","route":"/key-papers/paper-eng-imblaze370-atezolizumab-cobimetinib-colorectal-lancet-oncol-2019/","year":2019,"journal":"Lancet Oncology","paperType":"rct","tldr":"The phase 3 test of the idea that a MEK inhibitor could warm up an immunologically cold bowel cancer. It failed: neither immunotherapy alone nor the combination beat an existing pill.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-augment-lenalidomide-rituximab-leonard-jco-2019","kind":"paper","name":"AUGMENT: lenalidomide plus rituximab versus rituximab alone in relapsed indolent lymphoma","route":"/key-papers/paper-augment-lenalidomide-rituximab-leonard-jco-2019/","year":2019,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"Adding lenalidomide to rituximab more than doubled the time to progression in relapsed follicular and marginal zone lymphoma compared with rituximab alone, establishing a chemotherapy-free option for relapsed indolent lymphoma.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"paper-cassiopeia-lancet-2019","kind":"paper","name":"CASSIOPEIA: daratumumab added to bortezomib, thalidomide and dexamethasone before and after transplant in newly diagnosed myeloma","route":"/key-papers/paper-cassiopeia-lancet-2019/","year":2019,"journal":"The Lancet","paperType":"rct","tldr":"Adding the antibody daratumumab to a standard three-drug induction and consolidation around autologous transplant deepened responses and delayed progression in newly diagnosed myeloma, establishing four-drug induction.","via":[{"id":"daratumumab","kind":"drug","name":"Daratumumab","route":"/drugs/daratumumab/"}]},{"id":"paper-cll14-venetoclax-obinutuzumab-nejm-2019","kind":"paper","name":"CLL14: one year of venetoclax plus obinutuzumab instead of chemo-immunotherapy in older, less fit CLL patients","route":"/key-papers/paper-cll14-venetoclax-obinutuzumab-nejm-2019/","year":2019,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"A fixed one-year course of two targeted drugs kept CLL under control far longer than chemo-immunotherapy, and most patients had no detectable disease when treatment stopped.","via":[{"id":"obinutuzumab","kind":"drug","name":"Obinutuzumab","route":"/drugs/obinutuzumab/"}]},{"id":"paper-de-escalate-lancet-2019","kind":"paper","name":"De-ESCALaTE HPV: radiotherapy plus cisplatin or cetuximab in low-risk HPV-positive oropharyngeal cancer","route":"/key-papers/paper-de-escalate-lancet-2019/","year":2019,"journal":"The Lancet","paperType":"rct","tldr":"This European trial, like its American counterpart, found that replacing cisplatin with cetuximab in low-risk HPV-positive oropharyngeal cancer caused more recurrences and deaths without reducing severe toxicity.","via":[{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"}]},{"id":"paper-calgb-50303-da-epoch-r-vs-r-chop-jco-2019","kind":"paper","name":"Dose-adjusted EPOCH-R compared with R-CHOP as frontline therapy for diffuse large B-cell lymphoma: clinical outcomes of the phase III intergroup trial Alliance/CALGB 50303","route":"/key-papers/paper-calgb-50303-da-epoch-r-vs-r-chop-jco-2019/","year":2019,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"An intensive infusional chemotherapy regimen that many centres had adopted on single-arm evidence was no better than the standard when finally compared head to head, and was harder to tolerate.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"paper-paz-ares-caspian-durvalumab-es-sclc-lancet-2019","kind":"paper","name":"Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN)","route":"/key-papers/paper-paz-ares-caspian-durvalumab-es-sclc-lancet-2019/","year":2019,"journal":"The Lancet","paperType":"rct","tldr":"Adding immunotherapy to chemotherapy for advanced small-cell lung cancer raised median survival from 10.3 to 13.0 months. Small, but it was the second positive first-line trial in the disease in thirty years.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"},{"id":"tremelimumab","kind":"drug","name":"Tremelimumab","route":"/drugs/tremelimumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-oreilly-durvalumab-tremelimumab-pancreatic-jama-oncol-2019","kind":"paper","name":"Durvalumab with or without tremelimumab for patients with metastatic pancreatic ductal adenocarcinoma: a phase 2 randomized clinical trial","route":"/key-papers/paper-oreilly-durvalumab-tremelimumab-pancreatic-jama-oncol-2019/","year":2019,"journal":"JAMA Oncology","paperType":"rct","tldr":"Giving 65 patients with advanced pancreatic cancer a PD-L1 antibody alone or with a CTLA-4 antibody shrank tumours in 3% and 0%, so the trial was stopped before its second stage.","via":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"}]},{"id":"paper-marcoux-egfr-small-cell-transformation-outcomes-jco-2019","kind":"paper","name":"EGFR-mutant adenocarcinomas that transform to small-cell lung cancer and other neuroendocrine carcinomas: clinical outcomes","route":"/key-papers/paper-marcoux-egfr-small-cell-transformation-outcomes-jco-2019/","year":2019,"journal":"Journal of Clinical Oncology","paperType":"observational","tldr":"Sixty-seven patients whose lung cancer changed into small-cell carcinoma were followed across eight hospitals. The change came about a year and a half after diagnosis, chemotherapy worked well and immunotherapy did not work at all.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-kopetz-beacon-encorafenib-braf-colorectal-nejm-2019","kind":"paper","name":"Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer (BEACON CRC)","route":"/key-papers/paper-kopetz-beacon-encorafenib-braf-colorectal-nejm-2019/","year":2019,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"BRAF V600E bowel cancer had a median survival of four to six months after first-line failure. Blocking BRAF and EGFR together took it to nine, and made the doublet a standard.","via":[{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"paper-flyer-four-vs-six-cycles-r-chop-lancet-2019","kind":"paper","name":"Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER)","route":"/key-papers/paper-flyer-four-vs-six-cycles-r-chop-lancet-2019/","year":2019,"journal":"Lancet","paperType":"rct","tldr":"Young people with early, low-risk aggressive lymphoma did just as well with four rounds of chemotherapy as with six, and had roughly a quarter fewer side effects.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"paper-lenz-cms-calgb-swog-80405-jco-2019","kind":"paper","name":"Impact of consensus molecular subtype on survival in patients with metastatic colorectal cancer: results from CALGB/SWOG 80405","route":"/key-papers/paper-lenz-cms-calgb-swog-80405-jco-2019/","year":2019,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"In the one randomised trial where the four gene-activity subtypes were measured, they predicted not only how long people lived but which biological drug worked better: the immune subtype did better with bevacizumab and the canonical subtype with cetuximab.","via":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"},{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"}]},{"id":"paper-katherine-nejm-2019","kind":"paper","name":"KATHERINE: switching to T-DM1 when HER2-positive breast cancer survives pre-surgery treatment","route":"/key-papers/paper-katherine-nejm-2019/","year":2019,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Women whose HER2-positive breast cancer was still present at surgery after chemotherapy and trastuzumab had half the risk of relapse if their post-surgery treatment was switched to the antibody-drug conjugate T-DM1 instead of continuing trastuzumab.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-keynote-048-lancet-2019","kind":"paper","name":"KEYNOTE-048: pembrolizumab, alone or with chemotherapy, as first treatment for recurrent or metastatic head and neck cancer","route":"/key-papers/paper-keynote-048-lancet-2019/","year":2019,"journal":"The Lancet","paperType":"rct","tldr":"Pembrolizumab, either alone in PD-L1-positive tumours or combined with chemotherapy, helped patients with recurrent or metastatic head and neck squamous cell cancer live longer than the previous cetuximab-based standard.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-keynote-170-pembrolizumab-pmbcl-armand-jco-2019","kind":"paper","name":"KEYNOTE-170: pembrolizumab in relapsed or refractory primary mediastinal large B-cell lymphoma","route":"/key-papers/paper-keynote-170-pembrolizumab-pmbcl-armand-jco-2019/","year":2019,"journal":"Journal of Clinical Oncology","paperType":"observational","tldr":"Pembrolizumab produced responses in about 45 percent of patients with primary mediastinal B-cell lymphoma that had relapsed after chemotherapy, a lymphoma whose frequent 9p24.1 amplification makes it unusually sensitive to PD-1 blockade.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-keynote-426-nejm-2019","kind":"paper","name":"KEYNOTE-426: pembrolizumab plus axitinib versus sunitinib for advanced renal cell carcinoma","route":"/key-papers/paper-keynote-426-nejm-2019/","year":2019,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Combining pembrolizumab with the kinase inhibitor axitinib lengthened survival and delayed progression compared with sunitinib as first treatment for advanced clear cell kidney cancer, across all risk groups.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-maia-daratumumab-rd-nejm-2019","kind":"paper","name":"MAIA: adding daratumumab to lenalidomide-dexamethasone for older patients with newly diagnosed myeloma who cannot have a transplant","route":"/key-papers/paper-maia-daratumumab-rd-nejm-2019/","year":2019,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding the CD38 antibody daratumumab to standard lenalidomide-dexamethasone cut the risk of progression or death by about 44% in older myeloma patients, and later extended survival.","via":[{"id":"daratumumab","kind":"drug","name":"Daratumumab","route":"/drugs/daratumumab/"}]},{"id":"paper-rtog-1016-lancet-2019","kind":"paper","name":"NRG Oncology RTOG 1016: radiotherapy plus cetuximab versus cisplatin in HPV-positive oropharyngeal cancer","route":"/key-papers/paper-rtog-1016-lancet-2019/","year":2019,"journal":"The Lancet","paperType":"rct","tldr":"Trying to reduce toxicity by swapping cisplatin for cetuximab during radiotherapy in HPV-positive oropharyngeal cancer backfired: cetuximab gave worse survival and more recurrences with no reduction in toxicity, so cisplatin remains standard.","via":[{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"}]},{"id":"paper-takahashi-trastuzumab-docetaxel-salivary-duct-jco-2019","kind":"paper","name":"Phase 2 trial of trastuzumab and docetaxel in HER2-positive salivary duct carcinoma","route":"/key-papers/paper-takahashi-trastuzumab-docetaxel-salivary-duct-jco-2019/","year":2019,"journal":"Journal of Clinical Oncology","paperType":"observational","tldr":"In HER2-positive salivary duct carcinoma, an aggressive salivary cancer resembling breast cancer, trastuzumab plus docetaxel shrank tumours in 70 percent of patients, establishing HER2 testing and targeting in the disease.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-abida-msi-prostate-checkpoint-blockade-jama-oncol-2019","kind":"paper","name":"Prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade","route":"/key-papers/paper-abida-msi-prostate-checkpoint-blockade-jama-oncol-2019/","year":2019,"journal":"JAMA Oncology","paperType":"observational","tldr":"Three in a hundred prostate cancers have a broken proofreading system, and in the men who did, immunotherapy worked and kept working.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-phoenix-ibrutinib-r-chop-non-gcb-dlbcl-jco-2019","kind":"paper","name":"Randomized phase III trial of ibrutinib and R-CHOP in non-germinal centre B-cell diffuse large B-cell lymphoma (PHOENIX)","route":"/key-papers/paper-phoenix-ibrutinib-r-chop-non-gcb-dlbcl-jco-2019/","year":2019,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"Adding a targeted tablet to standard first-line chemotherapy failed overall, helped people under 60 substantially, and harmed people over 60 by making them unable to finish the chemotherapy.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"paper-prima-final-rituximab-maintenance-follicular-jco-2019","kind":"paper","name":"Sustained progression-free survival benefit of rituximab maintenance in patients with follicular lymphoma: long-term results of the PRIMA study","route":"/key-papers/paper-prima-final-rituximab-maintenance-follicular-jco-2019/","year":2019,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"After nine years the antibody maintenance group had gone more than six years longer before their lymphoma returned, and exactly as many people in each group were alive.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"paper-binnewies-tumor-immune-microenvironment-natmed-2018","kind":"paper","name":"Binnewies 2018: understanding the tumour immune microenvironment for effective therapy","route":"/key-papers/paper-binnewies-tumor-immune-microenvironment-natmed-2018/","year":2018,"journal":"Nature Medicine","paperType":"review","tldr":"A review that sorted tumours by where their immune cells sit, inflamed and infiltrated, infiltrated but excluded, or immune-poor, and argued that this classification should guide which immunotherapy a patient receives.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-gandara-blood-tmb-atezolizumab-nat-med-2018","kind":"paper","name":"Blood-based tumor mutational burden as a predictor of clinical benefit in non-small-cell lung cancer patients treated with atezolizumab","route":"/key-papers/paper-gandara-blood-tmb-atezolizumab-nat-med-2018/","year":2018,"journal":"Nature Medicine","paperType":"translational","tldr":"Counting mutations in a blood sample rather than in a piece of tumour identified the patients who gained most from one immunotherapy drug, which matters because many patients with advanced lung cancer have no tissue left to test.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-fader-trastuzumab-uterine-serous-jco-2018","kind":"paper","name":"Carboplatin-paclitaxel with or without trastuzumab in HER2-positive advanced or recurrent uterine serous carcinoma","route":"/key-papers/paper-fader-trastuzumab-uterine-serous-jco-2018/","year":2018,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"Adding trastuzumab to chemotherapy for HER2-positive uterine serous carcinoma, an aggressive endometrial cancer, lengthened progression-free survival by about four months and later showed a survival benefit, making HER2 testing routine in this subtype.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-checkmate-205-nivolumab-rr-hodgkin-extended-follow-up-jco-2018","kind":"paper","name":"CheckMate 205: nivolumab for relapsed or refractory classical Hodgkin lymphoma after autologous transplant failure, extended follow-up","route":"/key-papers/paper-checkmate-205-nivolumab-rr-hodgkin-extended-follow-up-jco-2018/","year":2018,"journal":"Journal of Clinical Oncology","paperType":"observational","tldr":"The PD-1 antibody nivolumab produced responses in about seven in ten patients whose Hodgkin lymphoma had returned after a stem cell transplant, with responses lasting well over a year, confirming the exquisite sensitivity of this lymphoma to checkpoint blockade.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"id":"paper-checkmate-214-nejm-2018","kind":"paper","name":"CheckMate 214: nivolumab plus ipilimumab versus sunitinib in advanced renal cell carcinoma","route":"/key-papers/paper-checkmate-214-nejm-2018/","year":2018,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Dual immunotherapy with nivolumab and ipilimumab lengthened survival compared with sunitinib in intermediate- and poor-risk advanced kidney cancer, with about one in ten patients achieving a complete response that has proved durable over years.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"id":"paper-arbour-kras-co-mutation-outcomes-ccr-2018","kind":"paper","name":"Effects of co-occurring genomic alterations on outcomes in patients with KRAS-mutant non-small cell lung cancer","route":"/key-papers/paper-arbour-kras-co-mutation-outcomes-ccr-2018/","year":2018,"journal":"Clinical Cancer Research","paperType":"observational","tldr":"Among 330 patients whose lung cancer carried a mutated KRAS gene, the ones who also had a broken KEAP1 gene did worse on every treatment: chemotherapy stopped working sooner and immunotherapy barely worked at all.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-hu-mismatch-repair-deficiency-pancreatic-adenocarcinoma-ccr-2018","kind":"paper","name":"Hu 2018: evaluating mismatch repair deficiency in pancreatic adenocarcinoma, challenges and recommendations","route":"/key-papers/paper-hu-mismatch-repair-deficiency-pancreatic-adenocarcinoma-ccr-2018/","year":2018,"journal":"Clinical Cancer Research","paperType":"observational","tldr":"Of more than 800 pancreatic cancers sequenced at one centre, under one in a hundred were mismatch repair deficient, most in people with Lynch syndrome, and several responded to immunotherapy. The paper set out how to test for the abnormality reliably in a cancer where standard tests often mislead.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-keynote-054-eggermont-nejm-2018","kind":"paper","name":"KEYNOTE-054 (EORTC 1325): adjuvant pembrolizumab versus placebo in resected stage III melanoma","route":"/key-papers/paper-keynote-054-eggermont-nejm-2018/","year":2018,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"A year of pembrolizumab after surgery for stage III melanoma cut the risk of recurrence by 43 percent compared with placebo, the first placebo-controlled proof that adjuvant PD-1 blockade works.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-keynote-189-nejm-2018","kind":"paper","name":"KEYNOTE-189: pembrolizumab plus chemotherapy as first treatment for non-squamous lung cancer without a driver mutation","route":"/key-papers/paper-keynote-189-nejm-2018/","year":2018,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding pembrolizumab to standard chemotherapy roughly halved the risk of death in newly diagnosed non-squamous lung cancer, whatever the PD-L1 level, making chemo-immunotherapy the default first treatment.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-mavoric-mogamulizumab-lancet-oncol-2018","kind":"paper","name":"MAVORIC: mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma","route":"/key-papers/paper-mavoric-mogamulizumab-lancet-oncol-2018/","year":2018,"journal":"The Lancet Oncology","paperType":"rct","tldr":"The anti-CCR4 antibody mogamulizumab doubled the time to progression compared with vorinostat in previously treated mycosis fungoides and Sezary syndrome, with particularly strong activity in the blood, and became the first antibody approved for these lymphomas.","via":[{"id":"mogamulizumab","kind":"drug","name":"Mogamulizumab","route":"/drugs/mogamulizumab/"}]},{"id":"paper-rizvi-targeted-ngs-immunotherapy-determinants-jco-2018","kind":"paper","name":"Molecular determinants of response to anti-PD-1 and anti-PD-L1 blockade in patients with non-small-cell lung cancer profiled with targeted next-generation sequencing","route":"/key-papers/paper-rizvi-targeted-ngs-immunotherapy-determinants-jco-2018/","year":2018,"journal":"Journal of Clinical Oncology","paperType":"observational","tldr":"The routine gene panel used in clinic can estimate how many mutations a lung cancer carries almost as well as sequencing the whole exome can, and tumours with more mutations were more likely to benefit from immunotherapy, independently of the PD-L1 stain.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-murano-venetoclax-rituximab-nejm-2018","kind":"paper","name":"MURANO: two years of venetoclax plus rituximab versus chemo-immunotherapy in relapsed CLL","route":"/key-papers/paper-murano-venetoclax-rituximab-nejm-2018/","year":2018,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"In relapsed CLL, a time-limited venetoclax-rituximab course cut progression risk by more than 80% compared with bendamustine-rituximab and later improved survival.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"paper-checkmate-227-n-engl-j-med-2018","kind":"paper","name":"Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden","route":"/key-papers/paper-checkmate-227-n-engl-j-med-2018/","year":2018,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Published report from the CheckMate 227 trial registered as NCT02477826, in New England Journal of Medicine (2018), chosen as the most cited paper whose own text cites the registry id.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-empower-cscc-1-cemiplimab-migden-nejm-2018","kind":"paper","name":"PD-1 blockade with cemiplimab in advanced cutaneous squamous cell carcinoma (EMPOWER-CSCC-1)","route":"/key-papers/paper-empower-cscc-1-cemiplimab-migden-nejm-2018/","year":2018,"journal":"New England Journal of Medicine","paperType":"observational","tldr":"Cemiplimab shrank tumours in about half of patients with metastatic or locally advanced cutaneous squamous cell carcinoma, a highly mutated skin cancer with almost no previous treatment options, leading to the first approval for the disease.","via":[{"id":"cemiplimab","kind":"drug","name":"Cemiplimab","route":"/drugs/cemiplimab/"}]},{"id":"paper-blueprint-phase-2-pd-l1-assays-jto-2018","kind":"paper","name":"PD-L1 immunohistochemistry comparability study in real-life clinical samples: results of Blueprint phase 2 project","route":"/key-papers/paper-blueprint-phase-2-pd-l1-assays-jto-2018/","year":2018,"journal":"Journal of Thoracic Oncology","paperType":"methods","tldr":"Five different stains for the same protein were run on 81 real lung cancer samples and read by pathologists from thirteen countries. Three of the five agree closely on tumour cells, one stains less and one stains more, and none of them can be read reliably on immune cells.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-giaccone-pembrolizumab-thymic-carcinoma-lancet-oncol-2018","kind":"paper","name":"Pembrolizumab in patients with thymic carcinoma: a single-arm phase 2 study","route":"/key-papers/paper-giaccone-pembrolizumab-thymic-carcinoma-lancet-oncol-2018/","year":2018,"journal":"The Lancet Oncology","paperType":"observational","tldr":"Immunotherapy shrank thymic carcinoma in about one patient in five after chemotherapy, but caused severe immune attacks on the heart and muscle more often than in other cancers, so it is used with care.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-trog-99-03-radiotherapy-systemic-therapy-early-follicular-jco-2018","kind":"paper","name":"Randomized trial of systemic therapy after involved-field radiotherapy in patients with early-stage follicular lymphoma: TROG 99.03","route":"/key-papers/paper-trog-99-03-radiotherapy-systemic-therapy-early-follicular-jco-2018/","year":2018,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"Adding six cycles of drug treatment after radiotherapy for early follicular lymphoma cut relapses outside the treated area and improved ten-year freedom from progression from 41 to 59 per cent.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"paper-relevance-rituximab-lenalidomide-follicular-lymphoma-morschhauser-nejm-2018","kind":"paper","name":"RELEVANCE: rituximab plus lenalidomide in advanced untreated follicular lymphoma","route":"/key-papers/paper-relevance-rituximab-lenalidomide-follicular-lymphoma-morschhauser-nejm-2018/","year":2018,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"A chemotherapy-free combination of rituximab and lenalidomide worked as well as rituximab with chemotherapy for untreated follicular lymphoma, though not better, with different side effects.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"paper-ribas-wolchok-checkpoint-blockade-science-2018","kind":"paper","name":"Ribas and Wolchok 2018: cancer immunotherapy using checkpoint blockade","route":"/key-papers/paper-ribas-wolchok-checkpoint-blockade-science-2018/","year":2018,"journal":"Science","paperType":"review","tldr":"A review by two of the field's leading trialists, written as checkpoint inhibitors reached a dozen cancers, explaining how CTLA-4 and PD-1 blockade work, why only some patients respond, and how resistance arises.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-kras-nsclc-cancer-discov-2018","kind":"paper","name":"STK11/LKB1 Mutations and PD-1 Inhibitor Resistance in KRAS -Mutant Lung Adenocarcinoma","route":"/key-papers/paper-kras-nsclc-cancer-discov-2018/","year":2018,"journal":"Cancer Discovery","paperType":"rct","tldr":"Phase 2 or 3 results paper on KRAS in Non-small-cell lung cancer, in Cancer Discovery (2018), one of the most cited Europe PMC records with KRAS in its title.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-juarez-ivermectin-repositioned-cancer-drug-2018","kind":"paper","name":"The multitargeted drug ivermectin: from an antiparasitic agent to a repositioned cancer drug","route":"/key-papers/paper-juarez-ivermectin-repositioned-cancer-drug-2018/","year":2018,"journal":"American Journal of Cancer Research","paperType":"review","tldr":"A 2018 review that gathered the cell-culture and animal experiments on ivermectin and argued it was ready for cancer trials; those trials began five years later and have not reported.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]},{"id":"paper-thorsson-immune-landscape-of-cancer-immunity-2018","kind":"paper","name":"Thorsson 2018: the immune landscape of cancer across 10,000 tumours","route":"/key-papers/paper-thorsson-immune-landscape-of-cancer-immunity-2018/","year":2018,"journal":"Immunity","paperType":"translational","tldr":"An analysis of more than 10,000 tumours from 33 cancer types in The Cancer Genome Atlas that sorted cancers into six immune subtypes, showing that the immune environment of a tumour cuts across its tissue of origin and affects prognosis.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-anbl1221-irinotecan-temozolomide-dinutuximab-mody-lancet-oncol-2017","kind":"paper","name":"ANBL1221: irinotecan-temozolomide with temsirolimus or dinutuximab in relapsed or refractory neuroblastoma","route":"/key-papers/paper-anbl1221-irinotecan-temozolomide-dinutuximab-mody-lancet-oncol-2017/","year":2017,"journal":"The Lancet Oncology","paperType":"rct","tldr":"In children whose neuroblastoma had come back, adding the anti-GD2 antibody dinutuximab to irinotecan and temozolomide shrank the cancer in half of them, while adding temsirolimus almost never did.","via":[{"id":"dinutuximab","kind":"drug","name":"Dinutuximab (ch14.18) / dinutuximab beta","route":"/drugs/dinutuximab/"}]},{"id":"paper-aphinity-nejm-2017","kind":"paper","name":"APHINITY: adjuvant pertuzumab added to trastuzumab and chemotherapy in early HER2-positive breast cancer","route":"/key-papers/paper-aphinity-nejm-2017/","year":2017,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding a second HER2 antibody, pertuzumab, to a year of trastuzumab after surgery reduced recurrences modestly in early HER2-positive breast cancer, with the gain concentrated in women with lymph node involvement.","via":[{"id":"pertuzumab","kind":"drug","name":"Pertuzumab","route":"/drugs/pertuzumab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-checkmate-026-first-line-nivolumab-nejm-2017","kind":"paper","name":"CheckMate 026: first-line nivolumab in stage IV or recurrent non-small-cell lung cancer","route":"/key-papers/paper-checkmate-026-first-line-nivolumab-nejm-2017/","year":2017,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Giving an immunotherapy drug instead of chemotherapy as the first treatment did not help patients selected only by a moderate level of the PD-L1 protein. It is the trial that showed the threshold, not the drug, was the problem.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-checkmate-238-nejm-2017","kind":"paper","name":"CheckMate 238: adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma","route":"/key-papers/paper-checkmate-238-nejm-2017/","year":2017,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"A year of adjuvant nivolumab after surgery for high-risk melanoma reduced recurrences more than the previous standard, high-dose ipilimumab, with a quarter of the severe toxicity, making PD-1 blockade the adjuvant standard.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"id":"paper-venook-calgb-80405-cetuximab-vs-bevacizumab-jama-2017","kind":"paper","name":"Effect of first-line chemotherapy combined with cetuximab or bevacizumab on overall survival in KRAS wild-type advanced or metastatic colorectal cancer (CALGB/SWOG 80405)","route":"/key-papers/paper-venook-calgb-80405-cetuximab-vs-bevacizumab-jama-2017/","year":2017,"journal":"JAMA","paperType":"rct","tldr":"The American head-to-head of the same two antibodies, in 1,137 patients, found no difference: 30.0 against 29.0 months. Read next to FIRE-3, it is why sidedness had to be invoked.","via":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"},{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"paper-ielsg-19-chlorambucil-rituximab-malt-jco-2017","kind":"paper","name":"Final results of the IELSG-19 randomized trial of mucosa-associated lymphoid tissue lymphoma: improved event-free and progression-free survival with rituximab plus chlorambucil versus either chlorambucil or rituximab monotherapy","route":"/key-papers/paper-ielsg-19-chlorambucil-rituximab-malt-jco-2017/","year":2017,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"The first randomised trial of first-line drug treatment for MALT lymphoma: the combination of an old tablet and an antibody beat either alone on relapse, and nobody lived longer.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"paper-gallium-obinutuzumab-first-line-follicular-lymphoma-marcus-nejm-2017","kind":"paper","name":"GALLIUM: obinutuzumab for the first-line treatment of follicular lymphoma","route":"/key-papers/paper-gallium-obinutuzumab-first-line-follicular-lymphoma-marcus-nejm-2017/","year":2017,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Obinutuzumab with chemotherapy and as maintenance kept follicular lymphoma from progressing for longer than rituximab, at the cost of more serious side effects.","via":[{"id":"obinutuzumab","kind":"drug","name":"Obinutuzumab","route":"/drugs/obinutuzumab/"},{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"paper-le-mmr-deficiency-science-2017","kind":"paper","name":"Le 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approval","route":"/key-papers/paper-le-mmr-deficiency-science-2017/","year":2017,"journal":"Science","paperType":"translational","tldr":"Across 86 patients with 12 different dMMR cancers, pembrolizumab produced responses in 53% and complete responses in 21%, prompting the first approval of a cancer drug based on a genetic marker rather than tumour site.","via":[{"id":"dostarlimab","kind":"drug","name":"Dostarlimab","route":"/drugs/dostarlimab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-remarc-lenalidomide-maintenance-dlbcl-jco-2017","kind":"paper","name":"Lenalidomide maintenance compared with placebo in responding elderly patients with diffuse large B-cell lymphoma treated with first-line R-CHOP","route":"/key-papers/paper-remarc-lenalidomide-maintenance-dlbcl-jco-2017/","year":2017,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"Two years of a tablet after chemotherapy delayed relapse in older people with aggressive lymphoma but did not help them live longer.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"paper-nci9673-nivolumab-metastatic-anal-cancer-morris-lancet-oncol-2017","kind":"paper","name":"NCI9673: nivolumab for previously treated unresectable metastatic anal cancer","route":"/key-papers/paper-nci9673-nivolumab-metastatic-anal-cancer-morris-lancet-oncol-2017/","year":2017,"journal":"The Lancet Oncology","paperType":"observational","tldr":"In the first completed immunotherapy trial for anal cancer, the PD-1 antibody nivolumab shrank tumours in a quarter of heavily pretreated patients with few side effects.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"id":"paper-dangelo-mucosal-melanoma-pooled-jco-2017","kind":"paper","name":"Nivolumab alone or with ipilimumab in mucosal melanoma: pooled analysis","route":"/key-papers/paper-dangelo-mucosal-melanoma-pooled-jco-2017/","year":2017,"journal":"Journal of Clinical Oncology","paperType":"observational","tldr":"Pooling several trials showed that mucosal melanoma responds to nivolumab less often than skin melanoma, but that adding ipilimumab raised the response rate from about a quarter to more than a third, supporting combination immunotherapy first.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"id":"paper-overman-checkmate-142-nivolumab-dmmr-colorectal-lancet-oncol-2017","kind":"paper","name":"Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142)","route":"/key-papers/paper-overman-checkmate-142-nivolumab-dmmr-colorectal-lancet-oncol-2017/","year":2017,"journal":"Lancet Oncology","paperType":"rct","tldr":"Seventy-four heavily pre-treated patients whose bowel cancers had lost DNA mismatch repair were given nivolumab; nearly a third responded and most of those responses were still going a year later.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-goya-obinutuzumab-vs-rituximab-chop-dlbcl-jco-2017","kind":"paper","name":"Obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in previously untreated diffuse large B-cell lymphoma","route":"/key-papers/paper-goya-obinutuzumab-vs-rituximab-chop-dlbcl-jco-2017/","year":2017,"journal":"Journal of 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40%.","via":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-ghsg-hd18-pet-guided-escalated-beacopp-lancet-2017","kind":"paper","name":"PET-guided treatment in patients with advanced-stage Hodgkin's lymphoma (HD18): final results of an open-label, international, randomised phase 3 trial by the German Hodgkin Study Group","route":"/key-papers/paper-ghsg-hd18-pet-guided-escalated-beacopp-lancet-2017/","year":2017,"journal":"Lancet","paperType":"rct","tldr":"People whose scan cleared after two rounds of the most intensive Hodgkin regimen could stop after four rounds instead of six or eight, halving severe infections with no loss of control.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"paper-tejpar-tumour-location-crystal-fire3-jama-oncol-2017","kind":"paper","name":"Prognostic and predictive relevance of primary tumor location in patients with RAS wild-type metastatic colorectal cancer: retrospective analyses of the CRYSTAL and FIRE-3 trials","route":"/key-papers/paper-tejpar-tumour-location-crystal-fire3-jama-oncol-2017/","year":2017,"journal":"JAMA Oncology","paperType":"rct","tldr":"Two European randomised trials, analysed separately, each showed the same thing: cetuximab helps left-sided bowel cancers with no RAS mutation and adds little on the right.","via":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"},{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"}]},{"id":"paper-arnold-primary-tumour-side-ras-wild-type-ann-oncol-2017","kind":"paper","name":"Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials","route":"/key-papers/paper-arnold-primary-tumour-side-ras-wild-type-ann-oncol-2017/","year":2017,"journal":"Annals of Oncology","paperType":"meta-analysis","tldr":"Pooling 2,159 patients from six trials showed that which side of the colon a tumour started on decides whether an EGFR antibody helps at all: a clear survival gain on the left, none on the right.","via":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"},{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"},{"id":"panitumumab","kind":"drug","name":"Panitumumab","route":"/drugs/panitumumab/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"paper-ptld-1-risk-stratified-sequential-treatment-trappe-jco-2017","kind":"paper","name":"PTLD-1: response to rituximab induction as a predictive marker allowing stratification into rituximab or R-CHOP consolidation in B-cell post-transplant lymphoproliferative disorder","route":"/key-papers/paper-ptld-1-risk-stratified-sequential-treatment-trappe-jco-2017/","year":2017,"journal":"Journal of Clinical Oncology","paperType":"observational","tldr":"In lymphoma arising after an organ transplant, starting with rituximab alone and then choosing between more rituximab and chemotherapy by response gave complete remission in seven of ten patients and a median survival of more than six years.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"paper-lyma-rituximab-maintenance-after-transplant-mantle-cell-nejm-2017","kind":"paper","name":"Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma","route":"/key-papers/paper-lyma-rituximab-maintenance-after-transplant-mantle-cell-nejm-2017/","year":2017,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Three years of an antibody every two months after a stem cell transplant kept younger people with mantle cell lymphoma in remission longer and helped them live longer.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"paper-sarc028-pembrolizumab-sarcoma-tawbi-lancet-oncol-2017","kind":"paper","name":"SARC028: pembrolizumab in advanced soft tissue and bone sarcoma","route":"/key-papers/paper-sarc028-pembrolizumab-sarcoma-tawbi-lancet-oncol-2017/","year":2017,"journal":"The Lancet Oncology","paperType":"observational","tldr":"Pembrolizumab had little effect in most sarcomas, but it shrank tumours in about 40 percent of patients with undifferentiated pleomorphic sarcoma and some with dedifferentiated liposarcoma, singling out these subtypes for immunotherapy.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-checkmate-141-ferris-nejm-2016","kind":"paper","name":"CheckMate 141: nivolumab for recurrent head and neck squamous cell carcinoma after platinum","route":"/key-papers/paper-checkmate-141-ferris-nejm-2016/","year":2016,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Nivolumab lengthened survival compared with standard single-agent chemotherapy in head and neck cancer that had progressed within six months of platinum treatment, the first immunotherapy to improve survival in the disease.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"id":"paper-sartore-bianchi-heracles-trastuzumab-lapatinib-lancet-oncol-2016","kind":"paper","name":"Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES)","route":"/key-papers/paper-sartore-bianchi-heracles-trastuzumab-lapatinib-lancet-oncol-2016/","year":2016,"journal":"The Lancet Oncology","paperType":"rct","tldr":"A trial designed from mouse avatars: screening 914 patients found 48 with HER2-amplified bowel cancer, and blocking HER2 two ways shrank tumours in 30 percent of the 27 who were treated.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"paper-ielsg32-matrix-induction-ferreri-lancet-haematol-2016","kind":"paper","name":"IELSG32 first randomisation: the MATRix regimen (methotrexate, cytarabine, thiotepa, rituximab) in primary CNS lymphoma","route":"/key-papers/paper-ielsg32-matrix-induction-ferreri-lancet-haematol-2016/","year":2016,"journal":"The Lancet Haematology","paperType":"rct","tldr":"Adding rituximab and thiotepa to methotrexate and cytarabine doubled the complete remission rate for lymphoma confined to the brain, making the four-drug MATRix regimen the standard induction for patients up to 70.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"paper-keynote-010-lancet-2016","kind":"paper","name":"KEYNOTE-010 (Herbst 2016): pembrolizumab versus docetaxel in previously treated PD-L1-positive lung cancer","route":"/key-papers/paper-keynote-010-lancet-2016/","year":2016,"journal":"The Lancet","paperType":"rct","tldr":"After chemotherapy had failed, pembrolizumab prolonged life compared with docetaxel in lung cancers expressing any PD-L1, with the largest gain in tumours where at least half the cells were positive, and caused fewer severe side effects.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-keynote-024-nejm-2016","kind":"paper","name":"KEYNOTE-024: pembrolizumab alone beats chemotherapy in PD-L1-high lung cancer","route":"/key-papers/paper-keynote-024-nejm-2016/","year":2016,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"In patients whose lung tumours carried PD-L1 on at least half their cells, pembrolizumab alone held the cancer back longer than chemotherapy and caused fewer serious side effects, making immunotherapy the first treatment for this group.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-apt-tolaney-nejm-2015","kind":"paper","name":"APT: adjuvant paclitaxel and trastuzumab for small, node-negative HER2-positive breast cancer","route":"/key-papers/paper-apt-tolaney-nejm-2015/","year":2015,"journal":"New England Journal of Medicine","paperType":"observational","tldr":"Twelve weeks of paclitaxel with a year of trastuzumab, and no anthracycline, was enough to keep more than 98 percent of women with small node-negative HER2-positive breast cancers free of recurrence at three years.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-valtorta-her2-scoring-colorectal-heracles-mod-pathol-2015","kind":"paper","name":"Assessment of a HER2 scoring system for colorectal cancer: results from a validation study","route":"/key-papers/paper-valtorta-her2-scoring-colorectal-heracles-mod-pathol-2015/","year":2015,"journal":"Modern Pathology","paperType":"methods","tldr":"Breast and stomach cancer HER2 scoring rules do not fit the bowel. This study wrote colorectal-specific criteria, tested them on more than a thousand samples, and produced the definition of HER2-positive that the trials have used ever since.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-checkmate-017-nejm-2015","kind":"paper","name":"CheckMate 017: nivolumab beats docetaxel in squamous lung cancer after chemotherapy","route":"/key-papers/paper-checkmate-017-nejm-2015/","year":2015,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"In squamous non-small-cell lung cancer that had progressed after platinum chemotherapy, the PD-1 antibody nivolumab prolonged life compared with docetaxel with far fewer severe side effects, regardless of PD-L1 status.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"id":"paper-checkmate-057-nejm-2015","kind":"paper","name":"CheckMate 057: nivolumab beats docetaxel after chemotherapy in non-squamous lung cancer","route":"/key-papers/paper-checkmate-057-nejm-2015/","year":2015,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"After platinum chemotherapy had failed, the PD-1 antibody nivolumab prolonged life compared with docetaxel in non-squamous lung cancer with far fewer severe side effects, and the benefit was largest in tumours expressing PD-L1.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"id":"paper-casulo-pod24-follicular-lymphoma-jco-2015","kind":"paper","name":"Early relapse of follicular lymphoma after R-CHOP defines patients at high risk for death: an analysis from the National LymphoCare Study","route":"/key-papers/paper-casulo-pod24-follicular-lymphoma-jco-2015/","year":2015,"journal":"Journal of Clinical Oncology","paperType":"observational","tldr":"One in five people whose follicular lymphoma came back within two years of first treatment had half the five-year survival of everyone else, which is why that two-year mark now changes the plan.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"paper-cremolini-tribe-folfoxiri-bevacizumab-lancet-oncol-2015","kind":"paper","name":"FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of TRIBE","route":"/key-papers/paper-cremolini-tribe-folfoxiri-bevacizumab-lancet-oncol-2015/","year":2015,"journal":"The Lancet Oncology","paperType":"rct","tldr":"Giving all three chemotherapy drugs at once rather than two added four months of life, and worked whatever the RAS or BRAF status. It is the most intensive first-line option for patients fit enough to take it.","via":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"}]},{"id":"paper-keynote-001-pembrolizumab-nsclc-nejm-2015","kind":"paper","name":"KEYNOTE-001 (Garon 2015): pembrolizumab in non-small-cell lung cancer and the 50% PD-L1 cut-off","route":"/key-papers/paper-keynote-001-pembrolizumab-nsclc-nejm-2015/","year":2015,"journal":"New England Journal of Medicine","paperType":"translational","tldr":"The large early trial that showed pembrolizumab shrinks about a fifth of advanced lung cancers, with responses that last, and that identified a PD-L1 score of 50% or more as the group most likely to benefit.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-keynote-006-pembrolizumab-ipilimumab-melanoma-nejm-2015","kind":"paper","name":"KEYNOTE-006 (Robert 2015): pembrolizumab versus ipilimumab in advanced melanoma","route":"/key-papers/paper-keynote-006-pembrolizumab-ipilimumab-melanoma-nejm-2015/","year":2015,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Head to head, the PD-1 antibody pembrolizumab held melanoma back longer, prolonged life and caused fewer severe side effects than ipilimumab, the CTLA-4 antibody that had been the first immunotherapy to extend survival.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-le-mmr-deficiency-pd1-nejm-2015","kind":"paper","name":"Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ","route":"/key-papers/paper-le-mmr-deficiency-pd1-nejm-2015/","year":2015,"journal":"New England Journal of Medicine","paperType":"translational","tldr":"Pembrolizumab shrank tumours in 40% of colorectal and 71% of other cancers with faulty DNA mismatch repair, but in none with intact repair, tying immunotherapy response to mutation burden.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-rizvi-mutational-landscape-pd1-science-2015","kind":"paper","name":"Rizvi 2015: the mutational landscape determines who responds to PD-1 blockade in lung cancer","route":"/key-papers/paper-rizvi-mutational-landscape-pd1-science-2015/","year":2015,"journal":"Science","paperType":"translational","tldr":"Lung cancers with more mutations, typically those caused by smoking, were more likely to respond to pembrolizumab, the study that established tumour mutational burden as a biomarker for immunotherapy.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-aurelia-bevacizumab-platinum-resistant-ovarian-pujade-lauraine-jco-2014","kind":"paper","name":"AURELIA: bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer","route":"/key-papers/paper-aurelia-bevacizumab-platinum-resistant-ovarian-pujade-lauraine-jco-2014/","year":2014,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"Adding bevacizumab to single-agent chemotherapy for platinum-resistant ovarian cancer doubled the time to progression and more than doubled the response rate, without a significant gain in survival.","via":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"}]},{"id":"paper-ozdemir-caf-depletion-accelerates-pancreatic-cancer-cancer-cell-2014","kind":"paper","name":"Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival","route":"/key-papers/paper-ozdemir-caf-depletion-accelerates-pancreatic-cancer-cancer-cell-2014/","year":2014,"journal":"Cancer Cell","paperType":"basic","tldr":"The 2014 mouse study showing that removing the scar-forming cells around pancreatic tumours made the cancers more aggressive and the mice die sooner, the warning that the stroma is not simply an obstacle to be cleared.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"}]},{"id":"paper-heinemann-fire-3-cetuximab-vs-bevacizumab-lancet-oncol-2014","kind":"paper","name":"FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3)","route":"/key-papers/paper-heinemann-fire-3-cetuximab-vs-bevacizumab-lancet-oncol-2014/","year":2014,"journal":"The Lancet Oncology","paperType":"rct","tldr":"A head-to-head of the two antibodies. They tied on response and progression, but patients on the EGFR antibody lived 3.7 months longer, a result nobody had predicted from the primary endpoint.","via":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"},{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"paper-gog-240-bevacizumab-cervical-nejm-2014","kind":"paper","name":"GOG 240: bevacizumab added to chemotherapy for advanced cervical cancer","route":"/key-papers/paper-gog-240-bevacizumab-cervical-nejm-2014/","year":2014,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding the anti-angiogenic antibody bevacizumab to chemotherapy lengthened survival by almost four months in recurrent or metastatic cervical cancer, the first targeted drug to improve survival in a gynaecological cancer.","via":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"}]},{"id":"paper-rainbow-ramucirumab-paclitaxel-lancet-oncol-2014","kind":"paper","name":"RAINBOW: ramucirumab plus paclitaxel versus placebo plus paclitaxel in previously treated advanced gastric cancer","route":"/key-papers/paper-rainbow-ramucirumab-paclitaxel-lancet-oncol-2014/","year":2014,"journal":"The Lancet Oncology","paperType":"rct","tldr":"Adding the anti-VEGFR2 antibody ramucirumab to weekly paclitaxel lengthened survival by over two months in gastric cancer that had progressed after first-line chemotherapy, establishing the standard second-line regimen.","via":[{"id":"ramucirumab","kind":"drug","name":"Ramucirumab","route":"/drugs/ramucirumab/"}]},{"id":"paper-tumeh-pd1-adaptive-immune-resistance-nature-2014","kind":"paper","name":"Tumeh 2014: PD-1 blockade works by releasing T cells already present at the tumour edge","route":"/key-papers/paper-tumeh-pd1-adaptive-immune-resistance-nature-2014/","year":2014,"journal":"Nature","paperType":"translational","tldr":"Melanomas that responded to pembrolizumab already contained killer T cells pressed up against tumour cells expressing PD-L1, showing that the drug works by releasing an immune attack that is already there rather than creating a new one.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-chen-mellman-cancer-immunity-cycle-immunity-2013","kind":"paper","name":"Chen and Mellman 2013: the cancer-immunity cycle","route":"/key-papers/paper-chen-mellman-cancer-immunity-cycle-immunity-2013/","year":2013,"journal":"Immunity","paperType":"review","tldr":"The seven-step diagram of how the immune system should destroy a cancer, from releasing tumour antigens to killing tumour cells, and the idea that each patient's cancer breaks the cycle at a different step, which tells you which immunotherapies to combine.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-dunleavy-da-epoch-r-pmbcl-nejm-2013","kind":"paper","name":"Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma","route":"/key-papers/paper-dunleavy-da-epoch-r-pmbcl-nejm-2013/","year":2013,"journal":"New England Journal of Medicine","paperType":"observational","tldr":"Infusional dose-adjusted EPOCH with rituximab cured almost every patient with primary mediastinal B-cell lymphoma without any radiotherapy, sparing young patients the heart and breast cancer risks of chest irradiation.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"paper-douillard-prime-panitumumab-ras-nejm-2013","kind":"paper","name":"Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer (PRIME)","route":"/key-papers/paper-douillard-prime-panitumumab-ras-nejm-2013/","year":2013,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Looking beyond the one KRAS exon everyone tested found that a further 17 percent of patients carried a RAS mutation and were harmed rather than helped by the antibody. Testing widened overnight.","via":[{"id":"panitumumab","kind":"drug","name":"Panitumumab","route":"/drugs/panitumumab/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"paper-misale-kras-acquired-resistance-anti-egfr-colorectal-nature-2012","kind":"paper","name":"Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer","route":"/key-papers/paper-misale-kras-acquired-resistance-anti-egfr-colorectal-nature-2012/","year":2012,"journal":"Nature","paperType":"translational","tldr":"Bowel cancers that respond to cetuximab almost always stop responding within a year. This paper showed why: KRAS-mutant cells take over, and their DNA shows up in the blood months before a scan changes.","via":[{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"},{"id":"panitumumab","kind":"drug","name":"Panitumumab","route":"/drugs/panitumumab/"}]},{"id":"paper-moreira-lynch-syndrome-identification-jama-2012","kind":"paper","name":"Identification of Lynch syndrome among patients with colorectal cancer","route":"/key-papers/paper-moreira-lynch-syndrome-identification-jama-2012/","year":2012,"journal":"JAMA","paperType":"meta-analysis","tldr":"Pooling four large studies, over 10,000 people with bowel cancer, showed that testing every tumour finds every case of the commonest inherited bowel cancer syndrome, while the clinical rules then in use missed about one in eight.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-pardoll-immune-checkpoint-blockade-nrc-2012","kind":"paper","name":"Pardoll 2012: the blockade of immune checkpoints in cancer immunotherapy","route":"/key-papers/paper-pardoll-immune-checkpoint-blockade-nrc-2012/","year":2012,"journal":"Nature Reviews Cancer","paperType":"review","tldr":"The review that named and organised the field of checkpoint blockade: tumours switch off attacking T cells through brakes such as CTLA-4 and PD-1, and antibodies that release those brakes can produce lasting responses.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-diaz-molecular-evolution-egfr-resistance-colorectal-nature-2012","kind":"paper","name":"The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers","route":"/key-papers/paper-diaz-molecular-evolution-egfr-resistance-colorectal-nature-2012/","year":2012,"journal":"Nature","paperType":"translational","tldr":"Published beside the paper above: resistance to EGFR antibodies does not have to be invented, it is already there. Rare KRAS-mutant cells present before treatment expand under it, on a schedule a mathematical model predicts.","via":[{"id":"panitumumab","kind":"drug","name":"Panitumumab","route":"/drugs/panitumumab/"}]},{"id":"paper-topalian-anti-pd1-nejm-2012","kind":"paper","name":"Topalian 2012: the first large trial of a PD-1 antibody shows durable responses across melanoma, lung and kidney cancer","route":"/key-papers/paper-topalian-anti-pd1-nejm-2012/","year":2012,"journal":"New England Journal of Medicine","paperType":"translational","tldr":"Nivolumab shrank tumours in roughly a fifth to a quarter of patients with three different advanced cancers, with responses that lasted more than a year and a hint that PD-L1 on the tumour predicted benefit.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-bertotti-xenopatients-her2-cetuximab-resistant-colorectal-cancer-discov-2011","kind":"paper","name":"A molecularly annotated platform of patient-derived xenografts identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer","route":"/key-papers/paper-bertotti-xenopatients-her2-cetuximab-resistant-colorectal-cancer-discov-2011/","year":2011,"journal":"Cancer Discovery","paperType":"translational","tldr":"Growing 85 patients' bowel cancers in mice and treating them like a clinical trial reproduced the pattern seen in people, and revealed that the tumours resisting cetuximab despite normal RAS often have extra copies of HER2.","via":[{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-crane-smad4-progression-pattern-locally-advanced-jco-2011","kind":"paper","name":"Phase II trial of cetuximab, gemcitabine, and oxaliplatin followed by chemoradiation with cetuximab for locally advanced (T4) pancreatic adenocarcinoma: correlation of Smad4(Dpc4) immunostaining with pattern of disease progression","route":"/key-papers/paper-crane-smad4-progression-pattern-locally-advanced-jco-2011/","year":2011,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"In 69 people with locally advanced pancreatic cancer, an ordinary Smad4 stain on the diagnostic needle sample predicted whether the cancer would grow locally or spread, the finding that supports using it to decide who gets radiotherapy.","via":[{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"}]},{"id":"paper-prima-rituximab-maintenance-follicular-lancet-2011","kind":"paper","name":"Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial","route":"/key-papers/paper-prima-rituximab-maintenance-follicular-lancet-2011/","year":2011,"journal":"Lancet","paperType":"rct","tldr":"Two years of an antibody given every two months after first-line chemotherapy raised the proportion still free of progression at three years from 58 to 75 per cent.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"paper-schreiber-cancer-immunoediting-science-2011","kind":"paper","name":"Schreiber, Old and Smyth 2011: cancer immunoediting","route":"/key-papers/paper-schreiber-cancer-immunoediting-science-2011/","year":2011,"journal":"Science","paperType":"review","tldr":"The review that set out the three Es of how the immune system shapes a cancer: elimination of many early tumours, an equilibrium in which growth is held in check, and escape when the tumour evolves ways to evade attack.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-hodi-ipilimumab-melanoma-nejm-2010","kind":"paper","name":"Hodi 2010: ipilimumab, the first checkpoint inhibitor, extends survival in metastatic melanoma","route":"/key-papers/paper-hodi-ipilimumab-melanoma-nejm-2010/","year":2010,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Blocking the immune brake CTLA-4 was the first treatment ever to prolong life in metastatic melanoma, with about one in five patients alive at two years and a new class of autoimmune side effects.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-royal-ipilimumab-pancreatic-j-immunother-2010","kind":"paper","name":"Phase 2 trial of single agent ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma","route":"/key-papers/paper-royal-ipilimumab-pancreatic-j-immunother-2010/","year":2010,"journal":"Journal of Immunotherapy","paperType":"rct","tldr":"The first checkpoint inhibitor trial in pancreatic cancer gave ipilimumab to 27 patients and not one tumour shrank by the standard measure, though one patient regressed later after apparent progression.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"}]},{"id":"paper-toga-trastuzumab-gastric-lancet-2010","kind":"paper","name":"ToGA (Bang 2010): trastuzumab with chemotherapy for HER2-positive advanced gastric cancer","route":"/key-papers/paper-toga-trastuzumab-gastric-lancet-2010/","year":2010,"journal":"The Lancet","paperType":"rct","tldr":"The trial that brought HER2 testing and trastuzumab to stomach cancer: adding the antibody to chemotherapy prolonged survival in patients whose gastric or junction cancers overexpressed HER2, about a fifth of those screened.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-van-cutsem-crystal-cetuximab-folfiri-nejm-2009","kind":"paper","name":"Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer (CRYSTAL)","route":"/key-papers/paper-van-cutsem-crystal-cetuximab-folfiri-nejm-2009/","year":2009,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"The trial that added an EGFR antibody to first-line chemotherapy and, in the same paper, showed the benefit belongs only to patients whose KRAS gene is normal. It is the first negative predictive biomarker in bowel cancer.","via":[{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"paper-plotkin-bevacizumab-nf2-nejm-2009","kind":"paper","name":"Hearing improvement after bevacizumab in patients with neurofibromatosis type 2","route":"/key-papers/paper-plotkin-bevacizumab-nf2-nejm-2009/","year":2009,"journal":"New England Journal of Medicine","paperType":"observational","tldr":"In a small series of people with NF2 and progressive vestibular schwannomas, the anti-VEGF antibody bevacizumab shrank the tumours in most and, remarkably, improved hearing in more than half, opening the first drug treatment for these tumours.","via":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"}]},{"id":"paper-extreme-vermorken-nejm-2008","kind":"paper","name":"EXTREME: platinum-based chemotherapy plus cetuximab in recurrent or metastatic head and neck cancer","route":"/key-papers/paper-extreme-vermorken-nejm-2008/","year":2008,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding cetuximab to platinum and fluorouracil lengthened survival in recurrent or metastatic head and neck cancer from 7.4 to 10.1 months, the first improvement in first-line treatment in decades.","via":[{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"}]},{"id":"paper-karapetis-kras-cetuximab-colorectal-nejm-2008","kind":"paper","name":"K-ras mutations and benefit from cetuximab in advanced colorectal cancer","route":"/key-papers/paper-karapetis-kras-cetuximab-colorectal-nejm-2008/","year":2008,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"The first randomised proof that a mutation can say a drug will not work: in a trial of cetuximab against supportive care alone, only patients whose tumours had a normal K-ras gene lived longer.","via":[{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"}]},{"id":"paper-sandler-ecog-4599-bevacizumab-nsclc-nejm-2006","kind":"paper","name":"Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer","route":"/key-papers/paper-sandler-ecog-4599-bevacizumab-nsclc-nejm-2006/","year":2006,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding an antibody against the tumour's blood supply to chemotherapy pushed median survival past a year for the first time in advanced lung cancer, at the cost of more treatment-related deaths.","via":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"}]},{"id":"paper-bonner-cetuximab-radiotherapy-nejm-2006","kind":"paper","name":"Radiotherapy plus cetuximab for locoregionally advanced squamous cell carcinoma of the head and neck","route":"/key-papers/paper-bonner-cetuximab-radiotherapy-nejm-2006/","year":2006,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding the EGFR antibody cetuximab to radiotherapy lengthened survival in locally advanced head and neck cancer by about 20 months without increasing the mucosal toxicity of radiotherapy, giving patients unfit for cisplatin an alternative.","via":[{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"}]},{"id":"paper-hurwitz-bevacizumab-crc-nejm-2004","kind":"paper","name":"Hurwitz 2004: bevacizumab with chemotherapy for metastatic colorectal cancer, the first anti-angiogenic drug to extend life","route":"/key-papers/paper-hurwitz-bevacizumab-crc-nejm-2004/","year":2004,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding the VEGF antibody bevacizumab to irinotecan-based chemotherapy prolonged survival in first-line metastatic colorectal cancer, the first time blocking a tumour's blood supply had been shown to help patients.","via":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"}]},{"id":"paper-coussens-werb-inflammation-cancer-nature-2002","kind":"paper","name":"Coussens and Werb 2002: inflammation and cancer","route":"/key-papers/paper-coussens-werb-inflammation-cancer-nature-2002/","year":2002,"journal":"Nature","paperType":"review","tldr":"The review that made the immune cells inside a tumour part of the disease: long-running inflammation, whether from infection, irritation or the tumour's own signals, supplies growth factors, blood vessels and DNA damage that help cancers start and spread.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-iwai-pdl1-tumour-escape-pnas-2002","kind":"paper","name":"Iwai and Honjo: tumours use PD-L1 to escape T cells, and blocking it restores attack","route":"/key-papers/paper-iwai-pdl1-tumour-escape-pnas-2002/","year":2002,"journal":"PNAS","paperType":"basic","tldr":"A decade after Honjo's group cloned PD-1 (1992), this study showed that tumour cells expressing PD-L1 resist killing by cytotoxic T cells in mice, and that anti-PD-L1 antibody or PD-1 deficiency restores tumour rejection, the foundation of PD-1/PD-L1 therapy.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-slamon-trastuzumab-nejm-2001","kind":"paper","name":"Slamon 2001: adding trastuzumab to chemotherapy for HER2-positive metastatic breast cancer","route":"/key-papers/paper-slamon-trastuzumab-nejm-2001/","year":2001,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"The trial that made trastuzumab standard: adding the HER2 antibody to chemotherapy slowed progression and prolonged life in women whose breast cancers overexpressed HER2, at the cost of heart weakening when it was paired with anthracyclines.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-leach-allison-ctla4-blockade-science-1996","kind":"paper","name":"Leach, Krummel and Allison: releasing the CTLA-4 brake makes mice reject tumours","route":"/key-papers/paper-leach-allison-ctla4-blockade-science-1996/","year":1996,"journal":"Science","paperType":"basic","tldr":"Injecting mice with an antibody that blocks the T-cell inhibitory receptor CTLA-4 caused established colon carcinomas and fibrosarcomas to be rejected and protected against re-challenge, the experiment that founded checkpoint immunotherapy.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]}],"eras":[{"roadmap":{"id":"colorectal-roadmap","kind":"roadmap","name":"Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation","route":"/roadmaps/colorectal-roadmap/"},"era":"2004-2017","title":"Antibodies, and the two things that decide whether they work","status":"current","step":5,"route":"/roadmaps/colorectal-roadmap/#story-step-4","refs":[{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"}]},{"roadmap":{"id":"colorectal-roadmap","kind":"roadmap","name":"Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation","route":"/roadmaps/colorectal-roadmap/"},"era":"2026-2032","title":"What the registry says is coming","status":"emerging","step":13,"route":"/roadmaps/colorectal-roadmap/#story-step-12","refs":[{"id":"dostarlimab","kind":"drug","name":"Dostarlimab","route":"/drugs/dostarlimab/"}]},{"roadmap":{"id":"ctdna-tests","kind":"roadmap","name":"ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment","route":"/roadmaps/ctdna-tests/"},"era":"2025-2026","title":"The first drug approval that depends on a ctDNA result","status":"current","step":6,"route":"/roadmaps/ctdna-tests/#story-step-5","refs":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"}]},{"roadmap":{"id":"devices-roadmap","kind":"roadmap","name":"Devices and physical therapies roadmap: heat and light → electric fields and focused sound → drug-releasing implants","route":"/roadmaps/devices-roadmap/"},"era":"2020-2026","title":"Light-activated drugs and drug-releasing implants","status":"current","step":4,"route":"/roadmaps/devices-roadmap/#story-step-3","refs":[{"id":"cetuximab-sarotalocan","kind":"drug","name":"Cetuximab sarotalocan","route":"/drugs/cetuximab-sarotalocan/"}]},{"roadmap":{"id":"gallbladder-cancer-roadmap","kind":"roadmap","name":"Gallbladder cancer roadmap: from a chance finding at gallstone surgery to a disease with its own trials","route":"/roadmaps/gallbladder-cancer-roadmap/"},"era":"2022-2025","title":"Immunotherapy joins chemotherapy","status":"current","step":7,"route":"/roadmaps/gallbladder-cancer-roadmap/#story-step-6","refs":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"roadmap":{"id":"global-access-roadmap","kind":"roadmap","name":"Global access and affordability roadmap: essential medicines and generics → biosimilars and frugal trials → reliance, pooling and homegrown innovation","route":"/roadmaps/global-access-roadmap/"},"era":"2012-2020","title":"Biosimilars and pooled procurement","status":"historic","step":2,"route":"/roadmaps/global-access-roadmap/#story-step-1","refs":[{"id":"trastuzumab-biosimilars","kind":"drug","name":"Trastuzumab biosimilars","route":"/drugs/trastuzumab-biosimilars/"}]},{"roadmap":{"id":"global-access-roadmap","kind":"roadmap","name":"Global access and affordability roadmap: essential medicines and generics → biosimilars and frugal trials → reliance, pooling and homegrown innovation","route":"/roadmaps/global-access-roadmap/"},"era":"2018-2026","title":"Homegrown innovation in India and China","status":"current","step":4,"route":"/roadmaps/global-access-roadmap/#story-step-3","refs":[{"id":"sintilimab","kind":"drug","name":"Sintilimab","route":"/drugs/sintilimab/"},{"id":"camrelizumab","kind":"drug","name":"Camrelizumab","route":"/drugs/camrelizumab/"}]},{"roadmap":{"id":"immunotherapy-roadmap","kind":"roadmap","name":"Immunotherapy roadmap: Coley's toxins → checkpoint inhibitors → engineered immunity","route":"/roadmaps/immunotherapy-roadmap/"},"era":"2011-2018","title":"Checkpoint revolution","status":"historic","step":2,"route":"/roadmaps/immunotherapy-roadmap/#story-step-1","refs":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"roadmap":{"id":"immunotherapy-roadmap","kind":"roadmap","name":"Immunotherapy roadmap: Coley's toxins → checkpoint inhibitors → engineered immunity","route":"/roadmaps/immunotherapy-roadmap/"},"era":"2018-2024","title":"Earlier lines and combinations","status":"current","step":3,"route":"/roadmaps/immunotherapy-roadmap/#story-step-2","refs":[{"id":"relatlimab-nivolumab","kind":"drug","name":"Relatlimab + nivolumab","route":"/drugs/relatlimab-nivolumab/"}]},{"roadmap":{"id":"paediatric-oncology-roadmap","kind":"roadmap","name":"Paediatric oncology roadmap: cooperative-group cures → engineered immunity → drugs developed for children first","route":"/roadmaps/paediatric-oncology-roadmap/"},"era":"1994-2015","title":"Immunotherapy for neuroblastoma, and counting the cost of cure","status":"historic","step":2,"route":"/roadmaps/paediatric-oncology-roadmap/#story-step-1","refs":[{"id":"dinutuximab","kind":"drug","name":"Dinutuximab (ch14.18) / dinutuximab beta","route":"/drugs/dinutuximab/"}]},{"roadmap":{"id":"pancreatic-roadmap","kind":"roadmap","name":"Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question","route":"/roadmaps/pancreatic-roadmap/"},"era":"What sets the pace","title":"Late presentation, fitness, wasting and who gets treated at all","status":"current","step":12,"route":"/roadmaps/pancreatic-roadmap/#story-step-11","refs":[{"id":"ponsegromab","kind":"drug","name":"Ponsegromab","route":"/drugs/ponsegromab/"}]},{"roadmap":{"id":"radiation-roadmap","kind":"roadmap","name":"Radiotherapy roadmap: X-rays → shaped beams → fewer fractions, particles and FLASH","route":"/roadmaps/radiation-roadmap/"},"era":"2017-2026","title":"Radiation plus drugs: what worked and what did not","status":"current","step":3,"route":"/roadmaps/radiation-roadmap/#story-step-2","refs":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"}]},{"roadmap":{"id":"targeted-therapy-roadmap","kind":"roadmap","name":"Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall","route":"/roadmaps/targeted-therapy-roadmap/"},"era":"1977-2001","title":"The idea of a target","status":"historic","step":1,"route":"/roadmaps/targeted-therapy-roadmap/#story-step-0","refs":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"roadmap":{"id":"tnbc-roadmap","kind":"roadmap","name":"Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem","route":"/roadmaps/tnbc-roadmap/"},"era":"2018-2024","title":"Immunotherapy: an assay dispute, then a new standard for early disease","status":"current","step":10,"route":"/roadmaps/tnbc-roadmap/#story-step-9","refs":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]}],"ideas":[{"id":"idea-fund-organ-preservation-programme","kind":"idea","name":"A funded programme of organ-preservation trials to avoid radical surgery","route":"/ideas/idea-fund-organ-preservation-programme/","maturity":"being-tested-at-scale","tldr":"For some cancers, drugs and radiotherapy can now cure without removing the organ, sparing patients a stoma, a lost voice or a removed bladder. A dedicated programme would run the trials to prove where this is safe.","via":[{"id":"dostarlimab","kind":"drug","name":"Dostarlimab","route":"/drugs/dostarlimab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-tr1-public-de-escalation-trial-fund","kind":"idea","name":"A public fund for trials that test less treatment","route":"/ideas/idea-tr1-public-de-escalation-trial-fund/","maturity":"being-tested-at-scale","tldr":"No company will pay to find out whether six months of its drug works as well as twelve. A dedicated public fund would pay for those trials, which save patients side effects and health systems money.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"idea-acc-risk-stratified-cardio-oncology-pathway","kind":"idea","name":"A risk-stratified cardio-oncology pathway for everyone receiving heart-toxic cancer therapy","route":"/ideas/idea-acc-risk-stratified-cardio-oncology-pathway/","maturity":"being-tested-at-scale","tldr":"Some chemotherapy and antibody drugs damage the heart. Checking heart function before and during treatment and starting protective drugs early for those at risk could prevent much of that damage.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"idea-post-neoadjuvant-adc","kind":"idea","name":"ADC for residual disease after KEYNOTE-522","route":"/ideas/idea-post-neoadjuvant-adc/","maturity":"being-tested-at-scale","tldr":"Patients whose TNBC survives chemo-immunotherapy before surgery have a high relapse risk. Give them an ADC after surgery.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-reg-biosimilar-no-efficacy-trial","kind":"idea","name":"Approve cancer biosimilars on analytics and pharmacokinetics, no efficacy trials","route":"/ideas/idea-reg-biosimilar-no-efficacy-trial/","maturity":"being-tested-at-scale","tldr":"Copies of biological cancer drugs are still required to run large trials that rarely change the answer. Dropping them would cut years and tens of millions from each biosimilar.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"idea-reg-market-expansion-repricing","kind":"idea","name":"Automatic price cuts when a cancer drug's approved indications and volumes expand","route":"/ideas/idea-reg-market-expansion-repricing/","maturity":"being-tested-at-scale","tldr":"When a cancer drug is approved for more uses, the company sells far more of it but the price stays the same. Japan cuts prices automatically when sales balloon; others should too.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-reg-biosimilar-first-default-switching","kind":"idea","name":"Biosimilar-first defaults and payment parity in every cancer day unit","route":"/ideas/idea-reg-biosimilar-first-default-switching/","maturity":"being-tested-at-scale","tldr":"Cheaper copies of biological cancer drugs exist but are used far less in some countries than others. Making them the default choice saves billions with no loss of benefit.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"idea-gbc-neoadjuvant-for-high-risk-incidental-cancer","kind":"idea","name":"Chemotherapy before the second operation for high-risk incidental gallbladder cancer","route":"/ideas/idea-gbc-neoadjuvant-for-high-risk-incidental-cancer/","maturity":"being-tested-at-scale","tldr":"Gallbladder cancers found by chance often come back within six months of the second operation, usually far from the gallbladder, which suggests the disease was already in the bloodstream. Two randomised trials are testing chemotherapy first; one closed small, the other reports in 2028.","via":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"}]},{"id":"lymphoma-ev-fixed-duration-chemotherapy-free-first-line","kind":"idea","name":"Fixed-duration, chemotherapy-free first-line treatment for the indolent lymphomas","route":"/ideas/lymphoma-ev-fixed-duration-chemotherapy-free-first-line/","maturity":"being-tested-at-scale","tldr":"Several treatments now work without chemotherapy, but most are given until the disease comes back. Giving them for a fixed time and stopping is the version patients would choose.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"idea-tnbc-de-escalation-for-exceptional-responders","kind":"idea","name":"Give exceptional responders less: pembrolizumab omission after complete response, anthracycline-free regimens and chemotherapy omission in lymphocyte-rich stage I disease","route":"/ideas/idea-tnbc-de-escalation-for-exceptional-responders/","maturity":"being-tested-at-scale","tldr":"Two thirds of women treated on the KEYNOTE-522 regimen have no tumour left at surgery and about 92 percent of them are alive without relapse at five years, yet all receive nine more cycles of pembrolizumab. Trials are now testing whether the best responders can stop early, skip the anthracycline, or in lymphocyte-rich stage I tumours skip chemotherapy altogether.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-acc-home-chemotherapy-older-patients","kind":"idea","name":"Home administration of selected chemotherapy and immunotherapy for older and frail patients","route":"/ideas/idea-acc-home-chemotherapy-older-patients/","maturity":"being-tested-at-scale","tldr":"For frail older patients, the journey to hospital can be the hardest part of treatment. Nurses can safely give some cancer treatments at home, which may help more people complete their course.","via":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"idea-cost-extended-interval-default","kind":"idea","name":"Make six-weekly immunotherapy the default schedule","route":"/ideas/idea-cost-extended-interval-default/","maturity":"being-tested-at-scale","tldr":"Pembrolizumab 400 mg every six weeks is approved and works like 200 mg every three weeks, and it halves the number of clinic visits, infusion chairs and travel days without changing the drug bill.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-cost-biosimilar-default-substitution","kind":"idea","name":"Make the biosimilar the default at the pharmacy for trastuzumab, bevacizumab and rituximab","route":"/ideas/idea-cost-biosimilar-default-substitution/","maturity":"being-tested-at-scale","tldr":"Copies of the big antibody drugs are approved and cheaper, but uptake depends on each prescriber; letting the pharmacy substitute the biosimilar unless the oncologist objects would move most patients within a year.","via":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"},{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"},{"id":"trastuzumab-biosimilars","kind":"drug","name":"Trastuzumab biosimilars","route":"/drugs/trastuzumab-biosimilars/"}]},{"id":"idea-molecular-class-adjuvant-endometrial","kind":"idea","name":"Molecular-class-directed adjuvant therapy in endometrial cancer","route":"/ideas/idea-molecular-class-adjuvant-endometrial/","maturity":"being-tested-at-scale","tldr":"Give adjuvant treatment by the tumour's molecular class rather than by stage and grade: nothing for POLE-mutated, immunotherapy for MMRd, chemotherapy plus targeted agents for p53-abnormal, hormones for NSMP.","via":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"}]},{"id":"idea-mrd-guided-stop-myeloma","kind":"idea","name":"MRD-guided treatment-free intervals in myeloma","route":"/ideas/idea-mrd-guided-stop-myeloma/","maturity":"being-tested-at-scale","tldr":"If a patient has had no detectable myeloma for a year or more, stop maintenance and watch, restarting only if disease reappears.","via":[{"id":"daratumumab","kind":"drug","name":"Daratumumab","route":"/drugs/daratumumab/"}]},{"id":"idea-organ-preservation-esophageal","kind":"idea","name":"Organ preservation as the default after complete response in oesophageal cancer","route":"/ideas/idea-organ-preservation-esophageal/","maturity":"being-tested-at-scale","tldr":"Oesophagectomy is one of the hardest operations in surgery. If chemoradiation (with or without immunotherapy) has made the tumour disappear, skip it and watch.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-reg-pooled-procurement-adult-essentials","kind":"idea","name":"Pooled international procurement of essential adult cancer medicines","route":"/ideas/idea-reg-pooled-procurement-adult-essentials/","maturity":"being-tested-at-scale","tldr":"Countries buying cancer drugs alone pay more and face shortages. Buying together, as they already do for childhood cancer drugs and vaccines, cuts prices and secures supply.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"idea-tr1-public-dose-reduction-trials-of-approved-drugs","kind":"idea","name":"Publicly funded dose-reduction trials of expensive approved drugs","route":"/ideas/idea-tr1-public-dose-reduction-trials-of-approved-drugs/","maturity":"being-tested-at-scale","tldr":"Some expensive approved cancer drugs probably work as well at lower doses, as reduced-dose abiraterone with food and extended-interval checkpoint inhibitors suggest. Companies will not test this, so payers should fund randomised non-inferiority trials prioritised by spend and pharmacology, and use the results in reimbursement.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-reg-public-deescalation-trials-for-cost","kind":"idea","name":"Publicly funded trials of lower and less frequent doses of expensive cancer drugs","route":"/ideas/idea-reg-public-deescalation-trials-for-cost/","maturity":"being-tested-at-scale","tldr":"Abiraterone at a quarter dose with food matches full-dose exposure, and pembrolizumab and nivolumab can be given at longer intervals, but no manufacturer will fund trials that cut its own revenue. A public 'value trials' fund would run non-inferiority trials of lower doses and longer intervals for the highest-spend cancer drugs, with payers committing to adopt positive results.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-crc-organ-preservation-randomised-in-pmmr-rectal","kind":"idea","name":"Randomise organ preservation against surgery in mismatch repair-proficient rectal cancer, with bowel function as a co-primary endpoint","route":"/ideas/idea-crc-organ-preservation-randomised-in-pmmr-rectal/","maturity":"being-tested-at-scale","tldr":"Half of rectal cancer patients given all their chemotherapy and radiotherapy first can keep their rectum. Nobody has ever randomised that against having the operation, so the trade-off between avoiding a stoma and the risk of the cancer regrowing is still guesswork.","via":[{"id":"dostarlimab","kind":"drug","name":"Dostarlimab","route":"/drugs/dostarlimab/"}]},{"id":"idea-tr1-immunotherapy-stop-trials","kind":"idea","name":"Randomised trials of stopping immunotherapy after one year versus continuing","route":"/ideas/idea-tr1-immunotherapy-stop-trials/","maturity":"being-tested-at-scale","tldr":"Immunotherapy is often given for two years or until it stops working, but responses can last long after stopping. Trials that randomly assign responders to stop or continue would show whether the extra year is needed.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-neoadjuvant-biomarker-engine","kind":"idea","name":"Use pre-surgery immunotherapy windows as the field's biomarker engine","route":"/ideas/idea-bio2-neoadjuvant-biomarker-engine/","maturity":"being-tested-at-scale","tldr":"Giving immunotherapy for a few weeks before surgery produces a tumour sample that shows exactly what the drug did. That is the fastest way to learn who responds.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-gbc-ctdna-residual-disease-guided-adjuvant-trial","kind":"idea","name":"A ctDNA residual disease-guided adjuvant trial after gallbladder cancer resection","route":"/ideas/idea-gbc-ctdna-residual-disease-guided-adjuvant-trial/","maturity":"early-clinical","tldr":"After surgery for bile duct or gallbladder cancer, a blood test for leftover tumour DNA picks out the people whose cancer will return with hazard ratios of 16 to 26 in two recent cohorts. Nobody has yet tested giving those people more than the standard capecitabine.","via":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"}]},{"id":"idea-acc-national-late-effects-registry","kind":"idea","name":"A national late-effects registry linking treatment exposures to outcomes decades later","route":"/ideas/idea-acc-national-late-effects-registry/","maturity":"early-clinical","tldr":"We know surprisingly little about what happens to cancer survivors twenty years on. Linking their treatment records to later health records would show which treatments cause which problems and who needs watching.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-fund-rt-io-platform","kind":"idea","name":"A neutral platform trial for radiotherapy plus immunotherapy combinations","route":"/ideas/idea-fund-rt-io-platform/","maturity":"early-clinical","tldr":"Radiotherapy may make immunotherapy work better, but the trials to test this are scattered and often small. One shared platform, run by radiotherapy groups with drugs supplied by several companies, would settle it faster.","via":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-tr2-tmb-calibration-standard","kind":"idea","name":"A single calibrated tumour mutational burden across all sequencing panels","route":"/ideas/idea-tr2-tmb-calibration-standard/","maturity":"early-clinical","tldr":"Tumour mutational burden decides who gets immunotherapy in some settings, but every sequencing panel calculates it differently. A shared calibration would make the number mean the same thing everywhere.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-adc-for-mesothelioma","kind":"idea","name":"Antibody-drug conjugates for mesothelioma: why they have failed so far and how they could work","route":"/ideas/idea-adc-for-mesothelioma/","maturity":"early-clinical","tldr":"Nearly every mesothelioma carries the surface protein mesothelin, yet the one antibody-drug conjugate tried in a randomised trial did no better than chemotherapy. The idea is to fix the three reasons it failed rather than abandon the approach.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-biomarker-quadruplet-gastric","kind":"idea","name":"Biomarker-directed first-line quadruplets in gastric cancer","route":"/ideas/idea-biomarker-quadruplet-gastric/","maturity":"early-clinical","tldr":"Stomach cancer now has three add-on biomarkers (HER2, PD-L1, Claudin 18.2) that often overlap. Test whether combining two add-ons beats picking one.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"tislelizumab","kind":"drug","name":"Tislelizumab","route":"/drugs/tislelizumab/"},{"id":"zolbetuximab","kind":"drug","name":"Zolbetuximab","route":"/drugs/zolbetuximab/"}]},{"id":"idea-moon-cardioprotection-by-default","kind":"idea","name":"Biomarker-guided cardioprotection for everyone on cardiotoxic cancer therapy","route":"/ideas/idea-moon-cardioprotection-by-default/","maturity":"early-clinical","tldr":"Anthracyclines, HER2 drugs and some newer agents can damage the heart. Monitor with blood tests and scans and start cheap heart-protective drugs early in those at risk.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"idea-adjuvant-selection-rcc","kind":"idea","name":"Biomarker-selected adjuvant therapy in RCC (ctDNA, CAIX PET, gene signatures)","route":"/ideas/idea-adjuvant-selection-rcc/","maturity":"early-clinical","tldr":"Adjuvant immunotherapy after kidney cancer surgery is given to everyone at high pathological risk although most would never relapse, so a year of toxicity is spread across the whole group to help a minority. A biomarker such as CAIX PET or kidney-specific tumour DNA could pick out the few who need it.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-bladder-preservation-mibc","kind":"idea","name":"Bladder preservation for MIBC after perioperative EV + pembrolizumab complete response","route":"/ideas/idea-bladder-preservation-mibc/","maturity":"early-clinical","tldr":"If the ADC-immunotherapy combination erases the tumour in more than half of patients before surgery, some may not need their bladder removed at all.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-atc-triplet-io","kind":"idea","name":"BRAF/MEK plus PD-1 blockade as standard for BRAF-mutant anaplastic thyroid cancer","route":"/ideas/idea-atc-triplet-io/","maturity":"early-clinical","tldr":"Add immunotherapy to the two targeted pills in the most aggressive thyroid cancer, because the combination has produced multi-year survivors in early series.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-tdxd-first-then-nothing","kind":"idea","name":"Can T-DXd alone cure early HER2-positive disease?","route":"/ideas/idea-tdxd-first-then-nothing/","maturity":"early-clinical","tldr":"If Enhertu produces complete responses in two-thirds of patients before surgery, a trial should test whether some need no chemotherapy, antibodies, or even radiation afterwards.","via":[{"id":"pertuzumab","kind":"drug","name":"Pertuzumab","route":"/drugs/pertuzumab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"idea-cd8-pet-io","kind":"idea","name":"CD8 PET to stop or switch immunotherapy early","route":"/ideas/idea-cd8-pet-io/","maturity":"early-clinical","tldr":"Scan for T cells inside the tumour a few weeks after starting immunotherapy. If they have not arrived, change course.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-chemo-free-hodgkin","kind":"idea","name":"Chemotherapy-free Hodgkin lymphoma: brentuximab + PD-1 in early stage","route":"/ideas/idea-chemo-free-hodgkin/","maturity":"early-clinical","tldr":"For a cancer already cured in 90% of young people, the goal is curing without the chemotherapy and radiation that cause heart disease and second cancers decades later.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-cxcr2-neutrophil-blockade","kind":"idea","name":"Clear the suppressive neutrophils out of pancreatic tumours first","route":"/ideas/idea-bio2-cxcr2-neutrophil-blockade/","maturity":"early-clinical","tldr":"Pancreatic tumours are packed with a type of white blood cell that shuts down the immune attack. Blocking the signal that recruits them may open the tumour to immunotherapy.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-gdf15-plus-exercise","kind":"idea","name":"Combine the new anti-wasting antibody with exercise and protein","route":"/ideas/idea-bio2-gdf15-plus-exercise/","maturity":"early-clinical","tldr":"A new antibody blocks the hormone that makes people with cancer lose appetite and weight. Weight regained as muscle, not fat, needs exercise and protein alongside it.","via":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"idea-tr1-low-dose-immunotherapy-for-lmic","kind":"idea","name":"Confirm ultra-low-dose immunotherapy so it can be afforded where most patients live","route":"/ideas/idea-tr1-low-dose-immunotherapy-for-lmic/","maturity":"early-clinical","tldr":"A single-centre trial at Tata Memorial found that adding nivolumab at about a twentieth of the usual dose to chemotherapy improved outcomes in head and neck cancer. Confirmatory trials against standard-dose immunotherapy are needed before low-dose labels could make immunotherapy affordable for millions.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-tnbc-ctdna-guided-adjuvant-decisions","kind":"idea","name":"ctDNA-guided adjuvant decisions after residual disease: escalate the positive, spare the negative","route":"/ideas/idea-tnbc-ctdna-guided-adjuvant-decisions/","maturity":"early-clinical","tldr":"After pre-surgery chemotherapy leaves tumour behind, a blood test for tumour DNA triples the risk of distant relapse when positive. The one trial that acted on it found the DNA usually appeared too late. A trial that tests at surgery with a tumour-informed assay, escalates positives to an antibody-drug conjugate and observes negatives has not been run.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-ctdna-guided-adjuvant-melanoma","kind":"idea","name":"ctDNA-guided adjuvant therapy in stage II-III melanoma","route":"/ideas/idea-ctdna-guided-adjuvant-melanoma/","maturity":"early-clinical","tldr":"Most stage II patients never relapse, yet all are offered a year of immunotherapy. Use a blood test to treat only those with detectable residual disease.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-pdac-cachexia-trials-embedded-in-chemotherapy-trials","kind":"idea","name":"Embed cachexia treatment in chemotherapy trials: weight, muscle and treatment delivery as co-primary endpoints","route":"/ideas/idea-pdac-cachexia-trials-embedded-in-chemotherapy-trials/","maturity":"early-clinical","tldr":"Most people with pancreatic cancer lose muscle and weight in a way food alone cannot reverse, and that wasting is a common reason chemotherapy is cut or stopped. A 2024 trial showed an antibody against the hormone GDF-15 restored weight and activity in twelve weeks, a third of the patients having pancreatic cancer. The proposal is to test it inside the chemotherapy trials, not alongside them.","via":[{"id":"ponsegromab","kind":"drug","name":"Ponsegromab","route":"/drugs/ponsegromab/"}]},{"id":"idea-tr1-extended-interval-checkpoint-dosing","kind":"idea","name":"Extended-interval immunotherapy: give checkpoint inhibitors every 8-12 weeks once stable","route":"/ideas/idea-tr1-extended-interval-checkpoint-dosing/","maturity":"early-clinical","tldr":"Immunotherapy antibodies stay active in the body for weeks, yet are often given every two or three weeks. After a few months, spacing doses out to every two or three months might work as well, with fewer hospital visits and much lower cost.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-tr2-combo-dose-matrix","kind":"idea","name":"Find the lowest effective doses of both drugs in a combination, not the highest tolerated","route":"/ideas/idea-tr2-combo-dose-matrix/","maturity":"early-clinical","tldr":"Combination trials usually keep one drug at full dose and push the other as high as patients can bear. Testing a grid of dose pairs would find combinations that work at lower, safer doses.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-cost-shorter-course-trials","kind":"idea","name":"Fund trials that test shorter courses of the most expensive adjuvant drugs","route":"/ideas/idea-cost-shorter-course-trials/","maturity":"early-clinical","tldr":"The PERSEPHONE trial showed six months of trastuzumab after surgery is as good as twelve, halving the drug cost; no company will run such trials, so public funders and charities must.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"idea-chronotherapy-immunotherapy","kind":"idea","name":"Give immunotherapy in the morning","route":"/ideas/idea-chronotherapy-immunotherapy/","maturity":"early-clinical","tldr":"Several studies found patients infused with checkpoint inhibitors earlier in the day lived longer. If a randomised trial confirms it, it is a free improvement available everywhere tomorrow.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-cost-subcutaneous-community","kind":"idea","name":"Give subcutaneous immunotherapy in community clinics and at home","route":"/ideas/idea-cost-subcutaneous-community/","maturity":"early-clinical","tldr":"Under-the-skin versions of atezolizumab, nivolumab and pembrolizumab take minutes rather than an hour and need no infusion chair, so they can be given by a nurse near home, cutting facility fees and travel.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-tnbc-pd-l1-assay-harmonisation","kind":"idea","name":"Harmonise PD-L1 testing for triple-negative breast cancer around one scored assay, with external quality assurance","route":"/ideas/idea-tnbc-pd-l1-assay-harmonisation/","maturity":"early-clinical","tldr":"Three PD-L1 tests run on the same tumours called 46, 75 and 73 percent of them positive and agreed only 69 percent of the time. With atezolizumab withdrawn, pembrolizumab's test (22C3, combined positive score of 10) is the only one that matters, yet laboratories still run whichever kit they have. One assay, one score and a proficiency scheme would end answers that vary by postcode.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-her2-adc-serous-endometrial","kind":"idea","name":"HER2 ADCs as standard for HER2-positive serous endometrial cancer","route":"/ideas/idea-her2-adc-serous-endometrial/","maturity":"early-clinical","tldr":"Serous endometrial cancers often overproduce HER2. Enhertu already works in them; testing HER2 in every p53-abnormal tumour and using the ADC earlier could change outcomes for the worst subtype.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"idea-tr1-home-infusion-trial-drugs","kind":"idea","name":"Home infusion and local blood draws for trial drugs after the first cycles","route":"/ideas/idea-tr1-home-infusion-trial-drugs/","maturity":"early-clinical","tldr":"Once a patient has safely had the first few doses of a trial drug at the hospital, later doses could be given at home or a local clinic, with blood tests done nearby, so distance no longer decides who can join.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"idea-hpv-ctdna-cervical","kind":"idea","name":"HPV circulating tumour DNA to guide cervical cancer therapy","route":"/ideas/idea-hpv-ctdna-cervical/","maturity":"early-clinical","tldr":"Because cervical tumours carry viral DNA that normal cells do not, a blood test for HPV DNA is a near-perfect tumour marker for tracking response and relapse.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-hcc-io-before-transplant","kind":"idea","name":"Immunotherapy downstaging to transplant with a safe washout","route":"/ideas/idea-hcc-io-before-transplant/","maturity":"early-clinical","tldr":"Use immunotherapy to shrink liver cancer enough for a transplant, and find the safe gap between the last dose and surgery so the new liver is not rejected.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-implantable-microdevice-screen","kind":"idea","name":"Implant a tiny device that tests twenty drugs inside the patient's own tumour","route":"/ideas/idea-bio2-implantable-microdevice-screen/","maturity":"early-clinical","tldr":"A rice-grain-sized implant releases microdoses of up to 20 drugs into separate spots of a tumour for one to three days, then is removed so pathologists can see which drug worked in that person's own tumour. First-in-human studies have been done in breast, sarcoma and brain tumours.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-immunotherapy-mss-crc","kind":"idea","name":"Making microsatellite-stable colorectal cancer immunotherapy-responsive","route":"/ideas/idea-immunotherapy-mss-crc/","maturity":"early-clinical","tldr":"Ninety-five percent of bowel cancers ignore immunotherapy. Combinations that heat the tumour up (targeted drugs, radiation, new checkpoints) are the main hope.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-histotripsy-immune-priming","kind":"idea","name":"Mechanically pulverise one tumour with ultrasound to wake the immune system","route":"/ideas/idea-bio2-histotripsy-immune-priming/","maturity":"early-clinical","tldr":"Focused ultrasound can break a tumour apart without heat or cuts, leaving debris the immune system can learn from. Doing that to one tumour may help treat the rest.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-neoadjuvant-adc-io","kind":"idea","name":"Neoadjuvant ADC + IO replacing anthracycline chemotherapy in TNBC","route":"/ideas/idea-neoadjuvant-adc-io/","maturity":"early-clinical","tldr":"Replace the toughest part of pre-surgery chemotherapy with an ADC plus immunotherapy, aiming for the same cure rate with less harm.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-neoadjuvant-io-glioblastoma","kind":"idea","name":"Neoadjuvant immunotherapy with surgical window for glioblastoma","route":"/ideas/idea-neoadjuvant-io-glioblastoma/","maturity":"early-clinical","tldr":"Give immunotherapy before surgery rather than after, so the tumour is still present to teach the immune system, then look inside it to learn what happened.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-tr2-contribution-of-components-mandate","kind":"idea","name":"No accelerated approval for a combination without proof each part contributes","route":"/ideas/idea-tr2-contribution-of-components-mandate/","maturity":"early-clinical","tldr":"Regulators should refuse to approve a two-drug combination unless there is evidence that both drugs are doing something, so patients are not exposed to useless extra toxicity and cost.","via":[{"id":"epacadostat","kind":"drug","name":"Epacadostat","route":"/drugs/epacadostat/"},{"id":"tiragolumab","kind":"drug","name":"Tiragolumab","route":"/drugs/tiragolumab/"}]},{"id":"idea-bio2-oncolytic-regulated-il12","kind":"idea","name":"Oncolytic viruses that make interleukin-12 only inside the tumour","route":"/ideas/idea-bio2-oncolytic-regulated-il12/","maturity":"early-clinical","tldr":"Interleukin-12 is an immune-stimulating cytokine that caused severe toxicity when injected into the bloodstream in the 1990s and was abandoned. An oncolytic herpes or adenovirus carrying the interleukin-12 gene under a drug-inducible promoter makes it only inside the tumour, keeping exposure local; trials include recurrent glioblastoma.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-tr2-pdl1-digital-calibration","kind":"idea","name":"One digital PD-L1 scale that maps across all the competing assays","route":"/ideas/idea-tr2-pdl1-digital-calibration/","maturity":"early-clinical","tldr":"There are several different PD-L1 tests, each tied to a different drug, and they disagree. A single digitally calibrated scale would let any lab's result be translated into any drug's cut-off.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-reg-indication-specific-pricing","kind":"idea","name":"Pay a different price for the same cancer drug depending on the indication","route":"/ideas/idea-reg-indication-specific-pricing/","maturity":"early-clinical","tldr":"One immunotherapy may add years of life in one cancer and weeks in another, yet costs the same. Prices should track the benefit in each use.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-fund-payer-funded-pragmatic-trials","kind":"idea","name":"Payers fund trials of cheaper, shorter or lower-dose versions of expensive treatments","route":"/ideas/idea-fund-payer-funded-pragmatic-trials/","maturity":"early-clinical","tldr":"Health insurers and national health systems have every reason to find out whether half the dose or half the duration of a costly drug works as well. They would fund those trials directly and keep the savings.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-photoimmunotherapy-plus-pd1","kind":"idea","name":"Photoimmunotherapy as an in situ vaccine with PD-1 blockade","route":"/ideas/idea-photoimmunotherapy-plus-pd1/","maturity":"early-clinical","tldr":"Bursting tumour cells with light releases their contents to the immune system; adding immunotherapy might turn a local treatment into a body-wide one.","via":[{"id":"cetuximab-sarotalocan","kind":"drug","name":"Cetuximab sarotalocan","route":"/drugs/cetuximab-sarotalocan/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-moon-pooled-procurement-licensing-pool","kind":"idea","name":"Pooled procurement and voluntary licensing for essential cancer medicines in low-income countries","route":"/ideas/idea-moon-pooled-procurement-licensing-pool/","maturity":"early-clinical","tldr":"Buy essential cancer drugs for many countries at once and license newer ones to generic makers, as was done for HIV, so prices fall to what those health systems can pay.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"idea-cost-indication-based-pricing","kind":"idea","name":"Price a cancer drug by how well it works in each cancer","route":"/ideas/idea-cost-indication-based-pricing/","maturity":"early-clinical","tldr":"A drug that adds a year of life in one cancer and six weeks in another sells at the same price for both; indication-specific prices would pay for the benefit actually delivered.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-bio2-antibiotic-stewardship-io","kind":"idea","name":"Protect the gut flora of patients about to start immunotherapy","route":"/ideas/idea-bio2-antibiotic-stewardship-io/","maturity":"early-clinical","tldr":"Antibiotics given in the weeks before immunotherapy are linked to much worse results. A simple stewardship rule could preserve benefit at no cost.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-fund-translational-institutes-gmp","kind":"idea","name":"Regional translational institutes with academic GMP suites and IND teams","route":"/ideas/idea-fund-translational-institutes-gmp/","maturity":"early-clinical","tldr":"Build a handful of publicly-funded centres where academic discoveries can be manufactured to clinical grade and written up for regulators, so good ideas do not die for lack of a factory and a filing.","via":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"idea-bio2-trem2-myeloid-reprogramming","kind":"idea","name":"Reprogramme suppressive macrophages instead of trying to delete them","route":"/ideas/idea-bio2-trem2-myeloid-reprogramming/","maturity":"early-clinical","tldr":"Tumours fill with immune cells that protect them. Earlier drugs tried to remove those cells and failed. Newer ones aim to switch them to the attacking side.","via":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-reg-weight-based-io-dosing-label","kind":"idea","name":"Restore weight-based dosing and vial sharing for immunotherapy in the label","route":"/ideas/idea-reg-weight-based-io-dosing-label/","maturity":"early-clinical","tldr":"Immunotherapy is given as one flat dose regardless of body size, which means smaller patients get more than they need. Dosing by weight would save a fifth of the drug at no cost to patients.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-tr1-model-based-dose-finding-with-late-toxicity","kind":"idea","name":"Retire the 3+3: model-based dose finding that counts late and chronic side effects","route":"/ideas/idea-tr1-model-based-dose-finding-with-late-toxicity/","maturity":"early-clinical","tldr":"The traditional way of finding a dose looks only at severe side effects in the first month. Modern statistical designs can use all patients' data and count the grumbling, long-lasting problems that make people quit months later.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-crc-mss-immunotherapy-by-biomarker-not-by-line","kind":"idea","name":"Select microsatellite stable patients for immunotherapy by a measured immune biomarker, not by how many treatments they have already failed","route":"/ideas/idea-crc-mss-immunotherapy-by-biomarker-not-by-line/","maturity":"early-clinical","tldr":"Ninety-five percent of advanced bowel cancers ignore immunotherapy, and the only real signal so far came in patients without active liver secondaries. Trials keep enrolling by treatment line rather than by immune biology, which guarantees the responders are diluted away.","via":[{"id":"balstilimab","kind":"drug","name":"Balstilimab","route":"/drugs/balstilimab/"},{"id":"botensilimab","kind":"drug","name":"Botensilimab","route":"/drugs/botensilimab/"},{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"id":"idea-reg-io-subscription-national","kind":"idea","name":"Subscription pricing for checkpoint inhibitors: fixed national fee, unlimited use","route":"/ideas/idea-reg-io-subscription-national/","maturity":"early-clinical","tldr":"Instead of paying per dose, a country would pay a fixed annual fee and treat every eligible patient with immunotherapy. This has worked for hepatitis C drugs and antibiotics.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-fmt-plus-checkpoint-phase3","kind":"idea","name":"Take faecal transplant plus immunotherapy to a definitive trial","route":"/ideas/idea-bio2-fmt-plus-checkpoint-phase3/","maturity":"early-clinical","tldr":"Transferring gut bacteria from patients who responded to immunotherapy has helped some patients who had stopped responding. It is time for a proper large trial.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-fibre-diet-io-trial","kind":"idea","name":"Test a high-fibre diet as an immunotherapy adjunct","route":"/ideas/idea-bio2-fibre-diet-io-trial/","maturity":"early-clinical","tldr":"People who eat more fibre appear to respond better to immunotherapy, while some probiotic supplements may do the opposite. A proper trial would settle it.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-tr1-weight-based-vs-flat-dosing-trials","kind":"idea","name":"Test flat versus weight-based dosing of antibodies, and use dose banding to cut waste","route":"/ideas/idea-tr1-weight-based-vs-flat-dosing-trials/","maturity":"early-clinical","tldr":"Monoclonal antibodies and ADCs have moved from weight-based to flat dosing on modelling alone, which is convenient but gives lighter patients relatively more drug. Randomised or pharmacokinetic comparisons, plus rounding doses to vial sizes where exposure is equivalent, could keep effectiveness while cutting cost and waste.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"idea-cost-low-dose-immunotherapy-trials","kind":"idea","name":"Test one-tenth-dose immunotherapy where the full dose is unaffordable","route":"/ideas/idea-cost-low-dose-immunotherapy-trials/","maturity":"early-clinical","tldr":"A randomised trial at Tata Memorial added nivolumab at 20 mg every three weeks, about one-twelfth of the standard dose, to cheap metronomic chemotherapy for head and neck cancer patients who could not afford full-dose immunotherapy, and they lived longer. Checkpoint inhibitors saturate their target far below approved doses, so publicly funded trials should test low doses in common cancers.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-steroid-sparing-irae","kind":"idea","name":"Treat immunotherapy side-effects without wiping out the response","route":"/ideas/idea-bio2-steroid-sparing-irae/","maturity":"early-clinical","tldr":"Immune side-effects are usually treated with high-dose steroids, which may also switch off the anti-cancer response. Targeted alternatives may control the side-effect and keep the benefit.","via":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-intracavitary-immunotherapy","kind":"idea","name":"Treat the body cavity, not the bloodstream, for surface spread","route":"/ideas/idea-bio2-intracavitary-immunotherapy/","maturity":"early-clinical","tldr":"Intracavitary immunotherapy targets cancer that coats the lining of the abdomen or chest, which drugs given by drip barely reach. Delivering it straight into the cavity gives far higher local doses.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-lymph-node-immune-priming","kind":"idea","name":"Treat the draining lymph node before removing it","route":"/ideas/idea-bio2-lymph-node-immune-priming/","maturity":"early-clinical","tldr":"The first lymph node cancer reaches is also where the immune system learns to fight it. Injecting immunotherapy into that node before surgery, instead of removing it blindly, may work better.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-in-situ-vaccination-solid","kind":"idea","name":"Turn one tumour into a vaccine to treat all the others","route":"/ideas/idea-bio2-in-situ-vaccination-solid/","maturity":"early-clinical","tldr":"Injecting immune-activating agents into a single tumour, plus a small dose of radiation, can teach the immune system to attack tumours elsewhere in the body.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-epigenetic-priming-cold-tumours","kind":"idea","name":"Unmask hidden antigens with a short epigenetic course before immunotherapy","route":"/ideas/idea-bio2-epigenetic-priming-cold-tumours/","maturity":"early-clinical","tldr":"Low doses of drugs that change how DNA is packaged can make cancer cells display more of what marks them as abnormal, potentially waking up immunotherapy in cold tumours.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-ctdna-six-week-io-switch","kind":"idea","name":"Use a blood test at six weeks to decide whether to keep going","route":"/ideas/idea-bio2-ctdna-six-week-io-switch/","maturity":"early-clinical","tldr":"Scans at three months often cannot tell whether immunotherapy is working. A blood test at six weeks may give a clearer, earlier answer.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-hypoxia-guided-adenosine","kind":"idea","name":"Use a hypoxia scan to pick patients for adenosine-pathway drugs","route":"/ideas/idea-bio2-hypoxia-guided-adenosine/","maturity":"early-clinical","tldr":"Tumours starved of oxygen produce a chemical that switches immune cells off. A scan can show which tumours are starved, and those are the ones to treat with blockers.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-vascular-normalisation-window","kind":"idea","name":"Use imaging to find the window when tumour blood vessels are working properly","route":"/ideas/idea-bio2-vascular-normalisation-window/","maturity":"early-clinical","tldr":"Low doses of anti-blood-vessel drugs briefly make tumour vessels work better, which helps immune cells and other drugs get in. Scans can find that window for each patient.","via":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-tr2-antagonism-surveillance","kind":"idea","name":"Watch routine care for drug combinations that quietly make cancer treatment worse","route":"/ideas/idea-tr2-antagonism-surveillance/","maturity":"early-clinical","tldr":"Some everyday medicines, such as antibiotics or steroids, seem to blunt immunotherapy. Automatically scanning health records for such harmful pairs would catch them years earlier.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-tcr-repertoire-early-readout","kind":"idea","name":"Watch the immune system's response in the blood three weeks in","route":"/ideas/idea-bio2-tcr-repertoire-early-readout/","maturity":"early-clinical","tldr":"When immunotherapy works, specific immune cell families multiply in the blood within weeks. Tracking that could tell patients early whether to continue.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-immune-exclusion-drivers","kind":"idea","name":"What actually holds T cells at the tumour border?","route":"/ideas/idea-immune-exclusion-drivers/","maturity":"early-clinical","tldr":"In immune-excluded tumours T cells reach the border but cannot get in, held back by fibroblasts, matrix, abnormal vessels, CXCL12 gradients or myeloid cells, and TGF-β drugs on their own have failed. If single-cell and spatial profiling can show which stromal programme dominates in each tumour, matching the drug (TGF-β, FAP, CXCR4 or VEGF) to it could let immunotherapy work.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-acc-biosimilar-prequalification-pool","kind":"idea","name":"WHO prequalification plus pooled demand to push biosimilar prices below 10% of the originator","route":"/ideas/idea-acc-biosimilar-prequalification-pool/","maturity":"early-clinical","tldr":"Biosimilars of trastuzumab, rituximab and bevacizumab have existed for years, but poorer countries cannot assess biologics themselves and place small fragmented orders. Extending WHO prequalification, begun with trastuzumab in 2019, to every oncology biosimilar and pooling procurement would give buyers assurance and makers volume, aiming below a tenth of originator prices.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"idea-bio2-tumour-anchored-tgfbeta-trap","kind":"idea","name":"Anchor a TGF-beta trap in the tumour stroma so it cannot act everywhere","route":"/ideas/idea-bio2-tumour-anchored-tgfbeta-trap/","maturity":"preclinical-evidence","tldr":"TGF-beta is a signal that keeps immune cells out of tumours, but blocking it throughout the body caused bleeding and heart toxicity and sank bintrafusp alfa. Tethering the blocker to tumour stroma with a FAP anchor, a collagen-binding domain or a protease-activated mask could give the benefit without the harm.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-myeloid-engager-bispecific","kind":"idea","name":"Bispecific antibodies that engage macrophages instead of T cells","route":"/ideas/idea-bio2-myeloid-engager-bispecific/","maturity":"preclinical-evidence","tldr":"Drugs that grab T cells and drag them onto tumours work well in blood cancers. The same trick aimed at tumour-eating cells might work where T cells are absent.","via":[{"id":"magrolimab","kind":"drug","name":"Magrolimab","route":"/drugs/magrolimab/"}]},{"id":"idea-bio2-complement-c5ar-blockade","kind":"idea","name":"Block the complement signal that recruits tumour-protecting cells","route":"/ideas/idea-bio2-complement-c5ar-blockade/","maturity":"preclinical-evidence","tldr":"An old part of the immune system called complement can be hijacked by tumours to summon protective cells. Drugs that block it already exist for other diseases.","via":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-antigen-presentation-triage","kind":"idea","name":"Check whether a tumour can still show itself to the immune system","route":"/ideas/idea-bio2-antigen-presentation-triage/","maturity":"preclinical-evidence","tldr":"Some tumours have broken the machinery that displays their identity to immune cells. Those patients cannot benefit from most immunotherapy and should be routed elsewhere.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-lactate-acid-axis","kind":"idea","name":"De-acidify the tumour so T cells can work in it","route":"/ideas/idea-bio2-lactate-acid-axis/","maturity":"preclinical-evidence","tldr":"Tumours are acidic, and immune cells stop working in acid. Neutralising that acid, or blocking the pumps that create it, might let immunotherapy work.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio1-evolutionary-double-bind","kind":"idea","name":"Design drug pairs where resisting one makes you vulnerable to the other","route":"/ideas/idea-bio1-evolutionary-double-bind/","maturity":"preclinical-evidence","tldr":"Choose two treatments so that whatever the tumour does to escape the first, it becomes easier to kill with the second. The immune system is a good candidate partner.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio1-lytac-surface-degraders","kind":"idea","name":"Drag cancer's surface and secreted proteins to the cell's recycling bin","route":"/ideas/idea-bio1-lytac-surface-degraders/","maturity":"preclinical-evidence","tldr":"Some cancer proteins sit on the cell surface or float outside cells, where protein-destroying drugs cannot reach. A different trick can drag them inside to be broken down.","via":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"idea-bio2-tertiary-lymphoid-induction","kind":"idea","name":"Grow immune command posts inside tumours","route":"/ideas/idea-bio2-tertiary-lymphoid-induction/","maturity":"preclinical-evidence","tldr":"Tumours that contain small immune structures resembling lymph nodes respond far better to immunotherapy. Inducing those structures on purpose could make cold tumours responsive.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio1-immune-matched-humanised-mice","kind":"idea","name":"Humanised mice with an immune system matched to the tumour donor","route":"/ideas/idea-bio1-immune-matched-humanised-mice/","maturity":"preclinical-evidence","tldr":"Most cancer drugs are tested in mice with no immune system, then given to people who have one. Mice carrying the same patient's immune cells and tumour would be a fairer test.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-moon-cold-to-hot-programme","kind":"idea","name":"Make every cold tumour hot: a coordinated programme to reprogramme immune-excluded tumours","route":"/ideas/idea-moon-cold-to-hot-programme/","maturity":"preclinical-evidence","tldr":"Immunotherapy works in tumours that immune cells can enter and ignores those that shut them out. Systematically test ways to open up the shut-out tumours, measured with spatial maps.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-radiotherapy-sting-fractionation","kind":"idea","name":"Pick the radiation dose that switches the immune alarm on, not off","route":"/ideas/idea-bio2-radiotherapy-sting-fractionation/","maturity":"preclinical-evidence","tldr":"Radiation can alert the immune system through the cGAS-STING pathway, but single doses above roughly 12 to 18 Gy switch on the enzyme TREX1, which destroys the alarm signal. Choosing fractionated schedules around 8 Gy times three for immune priming may add benefit at no extra cost.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-moon-irae-prediction-and-prevention","kind":"idea","name":"Predict immune side-effects before they happen and pre-empt them","route":"/ideas/idea-moon-irae-prediction-and-prevention/","maturity":"preclinical-evidence","tldr":"Immunotherapy can trigger dangerous attacks on the gut, lungs or heart. Use blood, gut bacteria and genetic markers to spot who is at risk and act early.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-reg-antihistamine-plus-io-trial","kind":"idea","name":"Randomise a cheap antihistamine alongside immunotherapy","route":"/ideas/idea-reg-antihistamine-plus-io-trial/","maturity":"preclinical-evidence","tldr":"Patients who happened to take common allergy pills during immunotherapy seemed to live longer in a large records study. A simple randomised trial would show whether the pills really help.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio1-aged-comorbid-models","kind":"idea","name":"Test cancer drugs in old and unhealthy animals, not just young fit ones","route":"/ideas/idea-bio1-aged-comorbid-models/","maturity":"preclinical-evidence","tldr":"Most cancer patients are older and have other illnesses, but nearly all animal experiments use young healthy mice. Results may not transfer.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio1-immunopeptidome-timing","kind":"idea","name":"Time immunotherapy to the moment targeted drugs make tumours visible","route":"/ideas/idea-bio1-immunopeptidome-timing/","maturity":"preclinical-evidence","tldr":"Targeted drugs briefly make cancer cells easier for the immune system to spot. Giving immunotherapy exactly in that window, rather than at the same time, may work better.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-trained-immunity-priming","kind":"idea","name":"Train the bone marrow to make better anti-tumour immune cells","route":"/ideas/idea-bio2-trained-immunity-priming/","maturity":"preclinical-evidence","tldr":"Certain vaccines and fungal sugars reprogramme the bone marrow so it produces more aggressive immune cells for months. That could be used before immunotherapy.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-fund-abbreviated-pathway-me-too-biologics","kind":"idea","name":"An abbreviated approval path for follow-on antibodies within a validated class","route":"/ideas/idea-fund-abbreviated-pathway-me-too-biologics/","maturity":"speculative","tldr":"Once a class of antibody such as PD-1 blockers is proven, later copies could be approved on smaller trials showing equivalence, forcing price competition and freeing patients and money for genuinely new drugs.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"idea-reg-pd1-biosimilar-advance-commitment","kind":"idea","name":"An advance market commitment for PD-1 biosimilars for lower-income countries","route":"/ideas/idea-reg-pd1-biosimilar-advance-commitment/","maturity":"speculative","tldr":"Immunotherapy patents start expiring around 2028. Guaranteeing in advance to buy cheap copies for poorer countries would make sure manufacturers build the capacity.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-fund-shelved-asset-escrow","kind":"idea","name":"Automatic offer of shelved cancer assets to non-profits after two years","route":"/ideas/idea-fund-shelved-asset-escrow/","maturity":"speculative","tldr":"When a company stops developing a cancer drug for business rather than safety reasons and leaves it idle for two years, it would be obliged to offer the rights, data package and remaining drug supply to qualified non-profit or academic developers on pre-set terms, keeping the right to resume. This turns the stalled-asset registry's listing into a duty.","via":[{"id":"magrolimab","kind":"drug","name":"Magrolimab","route":"/drugs/magrolimab/"},{"id":"tiragolumab","kind":"drug","name":"Tiragolumab","route":"/drugs/tiragolumab/"}]},{"id":"idea-nl-diet-covariates-io-trials","kind":"idea","name":"Capture diet, fibre and antibiotic exposure in every immunotherapy pivotal trial","route":"/ideas/idea-nl-diet-covariates-io-trials/","maturity":"speculative","tldr":"Gut bacteria appear to influence whether immunotherapy works, and diet and antibiotics shape gut bacteria. Yet almost no drug trial records what patients ate or which antibiotics they took. Recording it would cost almost nothing.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-fund-duration-trial-exclusivity","kind":"idea","name":"Extra exclusivity for sponsors who run treatment-duration and de-escalation trials","route":"/ideas/idea-fund-duration-trial-exclusivity/","maturity":"speculative","tldr":"Companies lose money when they prove a shorter course works, so they never test it. Give them a modest reward, such as extra months of exclusivity, when they do.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-tr1-factorial-dose-finding-for-combinations","kind":"idea","name":"Factorial dose finding for drug combinations instead of full dose of everything","route":"/ideas/idea-tr1-factorial-dose-finding-for-combinations/","maturity":"speculative","tldr":"When two cancer drugs are combined, each is usually given at its full single-agent dose, which often proves too toxic. Testing a grid of dose pairs would find combinations that work with tolerable side effects.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"lymphoma-ev-late-effects-of-the-treatments-given-now","kind":"idea","name":"Measure the late effects of the treatments being given now, not the ones given in 1975","route":"/ideas/lymphoma-ev-late-effects-of-the-treatments-given-now/","maturity":"speculative","tldr":"Everything known about the long-term cost of curing lymphoma comes from people treated decades ago with much larger radiation fields. Nobody knows the forty-year risks of what is given today.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-tr2-termination-reports","kind":"idea","name":"Public post-mortem reports when a cancer drug programme is stopped","route":"/ideas/idea-tr2-termination-reports/","maturity":"speculative","tldr":"When an aeroplane crashes, an independent report explains why so it does not happen again. When a cancer drug programme is abandoned, nothing is written. Change that.","via":[{"id":"epacadostat","kind":"drug","name":"Epacadostat","route":"/drugs/epacadostat/"},{"id":"magrolimab","kind":"drug","name":"Magrolimab","route":"/drugs/magrolimab/"}]},{"id":"idea-tr1-pk-informed-organ-thresholds","kind":"idea","name":"Replace fixed kidney and liver cut-offs with drug-specific, pharmacology-based thresholds","route":"/ideas/idea-tr1-pk-informed-organ-thresholds/","maturity":"speculative","tldr":"Most trials copy the same kidney and liver cut-offs, such as creatinine clearance above 60, regardless of how the drug is cleared. Setting each threshold from the drug's own clearance route and organ-impairment pharmacokinetic studies would let patients with mild organ impairment join safely instead of being excluded.","via":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"idea-fund-head-to-head-mandate","kind":"idea","name":"Require head-to-head trials against the best in class for later entrants","route":"/ideas/idea-fund-head-to-head-mandate/","maturity":"speculative","tldr":"Once two drugs of a kind exist, a third should have to prove itself against the best of them, not against an outdated comparison, so patients and payers learn which is actually better.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-fund-benefit-indexed-exclusivity","kind":"idea","name":"Shorter exclusivity for later-in-class drugs without added benefit","route":"/ideas/idea-fund-benefit-indexed-exclusivity/","maturity":"speculative","tldr":"The fifth PD-1 antibody that is no better than the first should not get the same market protection as the first. Exclusivity would shrink for copies that add nothing.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-bio2-protein-plus-training-during-io","kind":"idea","name":"Test protein and resistance training during immunotherapy","route":"/ideas/idea-bio2-protein-plus-training-during-io/","maturity":"speculative","tldr":"Muscle is an immune organ as well as a movement organ. Building it during immunotherapy might improve how well the treatment works, not just how patients feel.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"lymphoma-ev-the-drugs-that-cure-and-the-places-without-them","kind":"idea","name":"The drugs that cure lymphoma, and the places that do not have them","route":"/ideas/lymphoma-ev-the-drugs-that-cure-and-the-places-without-them/","maturity":"speculative","tldr":"Lymphoma is among the most curable common cancers where the drugs exist. Rituximab is thirty years old and still out of reach for many of the people who need it.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"idea-acc-eml-listing-price-commitments","kind":"idea","name":"Tie WHO essential-medicines listing to a published tiered price and supply pledge","route":"/ideas/idea-acc-eml-listing-price-commitments/","maturity":"speculative","tldr":"When a cancer drug is added to the WHO essential medicines list, the maker should publicly commit to a low price and reliable supply for poorer countries, or the listing is withheld.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]}],"manufacturing":{"sites":[{"id":"abzena-sanford","name":"Abzena Sanford","operator":"Abzena","operatorRoute":"/companies/abzena/","ownership":"cdmo","city":"Sanford, North Carolina","country":"US","capabilities":["adc-conjugation","antibody-drug-substance"],"capabilityLabels":["ADC 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