{"entity":{"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","aka":[],"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.","summary":"Patients with untreated stage IV or recurrent non-small-cell lung cancer and a PD-L1 tumour-expression level of 1% or more were randomly assigned to nivolumab or platinum-based chemotherapy. Among the 423 patients with a PD-L1 expression level of 5% or more, median progression-free survival was 4.2 months with nivolumab against 5.9 months with chemotherapy (hazard ratio 1.15) and median overall survival was 14.4 against 13.2 months (hazard ratio 1.02); 60% of the chemotherapy group crossed over to nivolumab. Treatment-related adverse events of grade 3 or 4 occurred in 18% with nivolumab and 51% with chemotherapy.","asOf":"2026-09-25","links":[{"label":"Carbone et al., N Engl J Med 2017: CheckMate 026, first-line nivolumab in PD-L1-positive non-small-cell lung cancer","url":"https://doi.org/10.1056/NEJMoa1613493"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28636851/"}],"tags":[],"related":["pd-l1-tc-score","tmb-high"],"cancers":["nsclc"],"sections":[],"technologies":["checkpoint-inhibitor","histopathology-ihc"],"targets":["pdl1","pd1"],"drugs":["nivolumab"],"companies":[],"institutions":[],"pathways":["pd1-checkpoint"],"terms":["tmb","ihc"],"trials":[],"people":["martin-reck"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/NEJMoa1613493","pmid":"28636851","authors":"Carbone DP, Reck M, Paz-Ares L, et al.","paperType":"rct","findings":["No progression-free survival benefit at a PD-L1 threshold of 5% or more, hazard ratio 1.15.","Overall survival similar, hazard ratio 1.02, with 60% crossover.","Far fewer grade 3 or 4 adverse events with nivolumab.","An exploratory high mutation burden subgroup did better, which did not rescue the trial."],"whatItMeans":"Read beside the pembrolizumab trial that succeeded at a 50% threshold in the same setting, it is the cleanest demonstration that a PD-L1 threshold is not a property of the protein but of the trial that drew the line.","caveats":["The comparison with the successful pembrolizumab trial is across trials, with different assays and populations.","Extensive crossover obscures the survival comparison.","The high burden subgroup analysis was exploratory and not powered."],"changedPractice":true,"participants":541},"route":"/key-papers/paper-checkmate-026-first-line-nivolumab-nejm-2017/","neighbours":{"biomarker":[{"id":"pd-l1-tc-score","kind":"biomarker","name":"PD-L1 TC score (tumour-cell score, SP263 and 28-8)","route":"/biomarkers/pd-l1-tc-score/"},{"id":"tmb-high","kind":"biomarker","name":"TMB-high (tumour mutational burden >= 10 mutations per megabase)","route":"/biomarkers/tmb-high/"}],"cancer":[{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/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":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}],"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":"tmb","kind":"term","name":"Tumour mutational burden (TMB)","route":"/terms/tmb/"}],"person":[{"id":"martin-reck","kind":"person","name":"Martin Reck","route":"/people/martin-reck/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}