{"entity":{"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","aka":[],"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.","summary":"This single-centre phase 2 study at Memorial Sloan Kettering treated patients with stage II or III mismatch-repair-deficient rectal adenocarcinoma with dostarlimab 500 mg every three weeks for six months, with the plan to proceed to chemoradiotherapy and surgery only if disease persisted. In the first 12 patients who completed treatment and had at least six months of follow-up, all had a clinical complete response on MRI, endoscopy, digital examination and biopsy, and none required chemoradiotherapy or surgery; no grade 3 or higher adverse events occurred. The follow-up report (NEJM 2025) extended the approach to more than 100 patients with dMMR cancers of several organs, with rectal cancer patients continuing to show near-universal complete responses and most avoiding surgery at two years.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa2201445"},{"label":"ClinicalTrials.gov NCT04165772","url":"https://clinicaltrials.gov/study/NCT04165772"}],"tags":[],"related":["paper-niche-2-nejm-2024","paper-le-mmr-deficiency-pd1-nejm-2015","msi-high","dmmr-ihc","colorectal-roadmap","paper-cercek-nonoperative-management-mismatch-repair-deficient-tumours-nejm-2025"],"cancers":["colorectal"],"sections":[],"technologies":["checkpoint-inhibitor","msi-mmr-testing","mri"],"targets":["pd1","mmr"],"drugs":["dostarlimab","pembrolizumab"],"companies":["gsk"],"institutions":["mskcc"],"pathways":["mismatch-repair-msi","pd1-checkpoint"],"terms":["msi","pcr","neoadjuvant-adjuvant","breakthrough-designation"],"trials":[],"people":["andrea-cercek","luis-diaz"],"bottlenecks":["b-surgery-radiation-innovation","b-toxicity-qol","b-immunotherapy-response"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2201445","authors":"Cercek A, Lumish M, Sinopoli J, et al.","paperType":"translational","findings":["12 patients with stage II-III dMMR rectal adenocarcinoma; dostarlimab 500 mg every 3 weeks for 6 months.","Clinical complete response in 12 of 12 (100%) at 6 months or more of follow-up.","No patient needed chemoradiotherapy or surgery; no recurrence at 6-25 months follow-up in the initial report.","No grade 3 or higher adverse events.","Larger follow-up (2025): sustained complete responses in the great majority of dMMR rectal cancer patients, and high rates of organ preservation across other dMMR tumour types."],"whatItMeans":"Cercek's dostarlimab study is the clearest demonstration that immunotherapy can replace surgery in a solid tumour: patients with dMMR rectal cancer can keep their rectum and avoid the permanent effects of pelvic radiotherapy and surgery. Non-operative management after PD-1 blockade is now in guidelines for this group, and MMR testing before treatment of rectal cancer is essential. The approach applies only to the 5-10% of rectal cancers that are dMMR.","caveats":["Small, single-centre, single-arm study; the 2022 report had only 12 patients and short follow-up.","Clinical complete response requires expert surveillance with MRI and endoscopy; salvage surgery must remain available.","Applies only to dMMR disease, a minority of rectal cancers.","Long-term durability beyond five years and late relapse risk are not yet known."],"changedPractice":true,"participants":12},"route":"/key-papers/paper-cercek-dostarlimab-rectal-nejm-2022/","neighbours":{"paper":[{"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/"},{"id":"paper-niche-2-nejm-2024","kind":"paper","name":"NICHE-2: a month of nivolumab and ipilimumab before surgery clears mismatch-repair-deficient colon cancer in most patients","route":"/key-papers/paper-niche-2-nejm-2024/"},{"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/"},{"id":"paper-habr-gama-nonoperative-stage-0-rectal-ann-surg-2004","kind":"paper","name":"Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results","route":"/key-papers/paper-habr-gama-nonoperative-stage-0-rectal-ann-surg-2004/"}],"biomarker":[{"id":"dmmr-ihc","kind":"biomarker","name":"dMMR (mismatch repair deficiency by IHC)","route":"/biomarkers/dmmr-ihc/"},{"id":"msi-high","kind":"biomarker","name":"MSI-high (microsatellite instability by PCR or sequencing)","route":"/biomarkers/msi-high/"}],"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/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"msi-high-colorectal","kind":"cancer","name":"Mismatch-repair deficient (MSI-high) colorectal cancer","route":"/cancers/msi-high-colorectal/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"mri","kind":"technology","name":"MRI","route":"/technologies/mri/"},{"id":"msi-mmr-testing","kind":"technology","name":"MSI and mismatch-repair testing","route":"/technologies/msi-mmr-testing/"}],"target":[{"id":"mmr","kind":"target","name":"Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2)","route":"/targets/mmr/"},{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"}],"drug":[{"id":"dostarlimab","kind":"drug","name":"Dostarlimab","route":"/drugs/dostarlimab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"company":[{"id":"gsk","kind":"company","name":"GSK","route":"/companies/gsk/"}],"institution":[{"id":"mskcc","kind":"institution","name":"Memorial Sloan Kettering Cancer Center","route":"/institutions/mskcc/"}],"pathway":[{"id":"mismatch-repair-msi","kind":"pathway","name":"Mismatch repair & microsatellite instability","route":"/pathways/mismatch-repair-msi/"},{"id":"pd1-checkpoint","kind":"pathway","name":"PD-1 / PD-L1 immune checkpoint & T-cell activation","route":"/pathways/pd1-checkpoint/"}],"term":[{"id":"breakthrough-designation","kind":"term","name":"Breakthrough Therapy / Priority Review / Priority Voucher","route":"/terms/breakthrough-designation/"},{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"},{"id":"neoadjuvant-adjuvant","kind":"term","name":"Neoadjuvant / adjuvant / perioperative","route":"/terms/neoadjuvant-adjuvant/"},{"id":"pcr","kind":"term","name":"Pathologic complete response (pCR)","route":"/terms/pcr/"}],"person":[{"id":"andrea-cercek","kind":"person","name":"Andrea Cercek","route":"/people/andrea-cercek/"},{"id":"julio-garcia-aguilar","kind":"person","name":"Julio Garcia-Aguilar","route":"/people/julio-garcia-aguilar/"},{"id":"luis-diaz","kind":"person","name":"Luis A. Diaz Jr.","route":"/people/luis-diaz/"}],"bottleneck":[{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"},{"id":"b-surgery-radiation-innovation","kind":"bottleneck","name":"Surgery and radiotherapy cure most, get least","route":"/bottlenecks/b-surgery-radiation-innovation/"},{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"idea":[{"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/"}]}}