{"entity":{"id":"keynote-042","kind":"trial","name":"KEYNOTE-042","aka":[],"tldr":"KEYNOTE-042 extended pembrolizumab alone to any lung cancer with at least 1 percent PD-L1, but the survival gain came almost entirely from the tumours with 50 percent or more, so chemotherapy is still added for the rest.","summary":"KEYNOTE-042 randomised 1,274 patients with untreated advanced non-small-cell lung cancer, no EGFR or ALK alteration and a PD-L1 tumour proportion score of at least 1 percent to pembrolizumab alone or to platinum-based chemotherapy. It asked whether the KEYNOTE-024 result in PD-L1-high disease extended down to lower expression.\n\nOverall survival favoured pembrolizumab in every prespecified group: median 20.0 versus 12.2 months in tumours with a score of 50 percent or more (hazard ratio 0.69), and 16.7 versus 12.1 months in the whole population with 1 percent or more (hazard ratio 0.81). In the exploratory group with scores of 1 to 49 percent, however, survival was no different (13.4 versus 12.1 months, hazard ratio 0.92).\n\nThe FDA widened the first-line monotherapy label to PD-L1 of 1 percent or more in April 2019, but guidelines reserve monotherapy for scores of 50 percent or more and pair pembrolizumab with chemotherapy below that, following KEYNOTE-189 and KEYNOTE-407.","status":"positive","asOf":"2026-09-17","links":[{"label":"ClinicalTrials.gov NCT02220894","url":"https://clinicaltrials.gov/study/NCT02220894"},{"label":"The Lancet 2019","url":"https://doi.org/10.1016/S0140-6736(18)32409-7"}],"tags":[],"related":[],"cancers":["nsclc","pdl1-high-nsclc"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pd1","pdl1"],"drugs":["pembrolizumab","carboplatin","paclitaxel","pemetrexed"],"companies":["merck"],"institutions":[],"pathways":["pd1-checkpoint"],"terms":["tps","pd-l1-testing"],"trials":[],"people":["tony-mok"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02220894","phase":"3","setting":"Untreated advanced non-small-cell lung cancer without EGFR or ALK alterations and PD-L1 tumour proportion score of 1 percent or more: pembrolizumab versus platinum doublet chemotherapy","sponsor":"Merck","result":"Median overall survival 20.0 vs 12.2 months (PD-L1 50% or more, hazard ratio 0.69); 16.7 vs 12.1 months (1% or more, hazard ratio 0.81); no difference at 1 to 49%.","yearReported":2019,"enrolled":1274,"outcomes":[{"endpoint":"Overall survival, PD-L1 tumour proportion score 50% or more","primary":true,"unit":"months","arms":[{"name":"Pembrolizumab","n":299,"value":20},{"name":"Platinum chemotherapy","n":300,"value":12.2}],"hr":0.69,"source":"https://doi.org/10.1016/S0140-6736(18)32409-7"},{"endpoint":"Overall survival, PD-L1 tumour proportion score 1% or more","primary":true,"unit":"months","arms":[{"name":"Pembrolizumab","n":637,"value":16.7},{"name":"Platinum chemotherapy","n":637,"value":12.1}],"hr":0.81,"source":"https://doi.org/10.1016/S0140-6736(18)32409-7"}],"replication":"Consistent with KEYNOTE-024 in the PD-L1-high group; IMpower110 (atezolizumab) and EMPOWER-Lung 1 (cemiplimab) showed the same pattern of benefit concentrated in high expressers."},"route":"/trials/keynote-042/","neighbours":{"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":"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":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"paclitaxel","kind":"drug","name":"Paclitaxel / nab-paclitaxel","route":"/drugs/paclitaxel/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"pemetrexed","kind":"drug","name":"Pemetrexed","route":"/drugs/pemetrexed/"}],"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":"pd-l1-testing","kind":"term","name":"PD-L1 expression testing (22C3, SP142, SP263)","route":"/terms/pd-l1-testing/"},{"id":"tps","kind":"term","name":"Tumour proportion score (TPS)","route":"/terms/tps/"}],"person":[{"id":"tony-mok","kind":"person","name":"Tony S. K. Mok","route":"/people/tony-mok/"}]}}