{"entity":{"id":"paper-keynote-024-nejm-2016","kind":"paper","name":"KEYNOTE-024: pembrolizumab alone beats chemotherapy in PD-L1-high lung cancer","aka":[],"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.","summary":"KEYNOTE-024 randomised 305 patients with untreated advanced non-small-cell lung cancer, a PD-L1 tumour proportion score of 50% or more and no EGFR or ALK alteration to pembrolizumab or platinum-based chemotherapy. Pembrolizumab improved progression-free survival, the primary endpoint, and overall survival at the interim analysis, with a higher response rate and fewer grade 3 to 5 adverse events, and patients on chemotherapy could cross over at progression. Five-year follow-up later confirmed the survival advantage. The trial made PD-L1 testing routine at lung cancer diagnosis and established chemotherapy-free first-line immunotherapy for the PD-L1-high group.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1606774"},{"label":"ClinicalTrials.gov NCT02142738","url":"https://clinicaltrials.gov/study/NCT02142738"}],"tags":[],"related":["lung-cancer-evidence-roadmap","paper-herbst-impower110-atezolizumab-pd-l1-nejm-2020","pd-l1-tps"],"cancers":["nsclc","lung-cancer"],"sections":[],"technologies":["histopathology-ihc","checkpoint-inhibitor"],"targets":["pd1","pdl1"],"drugs":["pembrolizumab"],"companies":["merck"],"institutions":[],"pathways":["pd1-checkpoint"],"terms":["tps","pfs","os","ihc"],"trials":["keynote-024-189"],"people":["martin-reck"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2016,"doi":"10.1056/NEJMoa1606774","authors":"Reck M, Rodríguez-Abreu D, Robinson AG, et al.","paperType":"rct","findings":["305 patients with PD-L1 tumour proportion score of 50% or more; pembrolizumab vs platinum doublet chemotherapy.","Median progression-free survival 10.3 vs 6.0 months, hazard ratio 0.50.","Overall survival hazard ratio 0.60 at the interim analysis; estimated six-month survival 80.2% vs 72.4%.","Response rate 44.8% vs 27.8%; grade 3 to 5 treatment-related adverse events 26.6% vs 53.3%."],"whatItMeans":"This trial is why PD-L1 is measured on every new advanced lung cancer and why a patient with a high score can start immunotherapy without chemotherapy. Together with KEYNOTE-189 for the rest of the population, it moved checkpoint inhibitors from second-line rescue to the first treatment most lung cancer patients receive.","caveats":["Applies only to the roughly 30% of patients with a PD-L1 score of 50% or more and no EGFR or ALK driver.","Crossover from chemotherapy to pembrolizumab affected the survival comparison.","PD-L1 testing varies by assay and is imperfect as a predictor within the eligible group."],"changedPractice":true,"participants":305},"route":"/key-papers/paper-keynote-024-nejm-2016/","neighbours":{"roadmap":[{"id":"lung-cancer-evidence-roadmap","kind":"roadmap","name":"Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch","route":"/roadmaps/lung-cancer-evidence-roadmap/"}],"paper":[{"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/"},{"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/"},{"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/"}],"biomarker":[{"id":"pd-l1-tps","kind":"biomarker","name":"PD-L1 TPS (tumour proportion score)","route":"/biomarkers/pd-l1-tps/"}],"cancer":[{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"pdl1-high-nsclc","kind":"cancer","name":"PD-L1-high non-small-cell lung cancer without a driver mutation","route":"/cancers/pdl1-high-nsclc/"}],"technology":[{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"target":[{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"},{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"}],"drug":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"company":[{"id":"merck","kind":"company","name":"Merck & Co. (MSD)","route":"/companies/merck/"}],"pathway":[{"id":"pd1-checkpoint","kind":"pathway","name":"PD-1 / PD-L1 immune checkpoint & T-cell activation","route":"/pathways/pd1-checkpoint/"}],"term":[{"id":"ihc","kind":"term","name":"Immunohistochemistry (IHC)","route":"/terms/ihc/"},{"id":"os","kind":"term","name":"Overall survival (OS)","route":"/terms/os/"},{"id":"pfs","kind":"term","name":"Progression-free survival (PFS)","route":"/terms/pfs/"},{"id":"tps","kind":"term","name":"Tumour proportion score (TPS)","route":"/terms/tps/"}],"trial":[{"id":"keynote-024-189","kind":"trial","name":"KEYNOTE-024 & KEYNOTE-189","route":"/trials/keynote-024-189/"}],"person":[{"id":"martin-reck","kind":"person","name":"Martin Reck","route":"/people/martin-reck/"}],"idea":[{"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/"},{"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/"}]}}