{"doi":"10.1016/s0140-6736(15)01281-7","title":"Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial","abstract":"<h4>Background</h4>Despite recent advances in the treatment of advanced non-small-cell lung cancer, there remains a need for effective treatments for progressive disease. We assessed the efficacy of pembrolizumab for patients with previously treated, PD-L1-positive, advanced non-small-cell lung cancer.<h4>Methods</h4>We did this randomised, open-label, phase 2/3 study at 202 academic medical centres in 24 countries. Patients with previously treated non-small-cell lung cancer with PD-L1 expression on at least 1% of tumour cells were randomly assigned (1:1:1) in blocks of six per stratum with an interactive voice-response system to receive pembrolizumab 2 mg/kg, pembrolizumab 10 mg/kg, or docetaxel 75 mg/m(2) every 3 weeks. The primary endpoints were overall survival and progression-free survival both in the total population and in patients with PD-L1 expression on at least 50% of tumour cells. We used a threshold for significance of p<0.00825 (one-sided) for the analysis of overall survival and a threshold of p<0.001 for progression-free survival. This trial is registered at ClinicalTrials.gov, number NCT01905657.<h4>Findings</h4>Between Aug 28, 2013, and Feb 27, 2015, we enrolled 1034 patients: 345 allocated to pembrolizumab 2 mg/kg, 346 allocated to pembrolizumab 10 mg/kg, and 343 allocated to docetaxel. By Sept 30, 2015, 521 patients had died. In the total population, median overall survival was 10.4 months with pembrolizumab 2 mg/kg, 12.7 months with pembrolizumab 10 mg/kg, and 8.5 months with docetaxel. Overall survival was significantly longer for pembrolizumab 2 mg/kg versus docetaxel (hazard ratio [HR] 0.71, 95% CI 0.58-0.88; p=0.0008) and for pembrolizumab 10 mg/kg versus docetaxel (0.61, 0.49-0.75; p<0.0001). Median progression-free survival was 3.9 months with pembrolizumab 2 mg/kg, 4.0 months with pembrolizumab 10 mg/kg, and 4.0 months with docetaxel, with no significant difference for pembrolizumab 2 mg/kg versus docetaxel (0.88, 0.74-1.05; p=0.07) or for pembrolizumab 10 mg/kg versus docetaxel (HR 0.79, 95% CI 0.66-0.94; p=0.004). Among patients with at least 50% of tumour cells expressing PD-L1, overall survival was significantly longer with pembrolizumab 2 mg/kg than with docetaxel (median 14.9 months vs 8.2 months; HR 0.54, 95% CI 0.38-0.77; p=0.0002) and with pembrolizumab 10 mg/kg than with docetaxel (17.3 months vs 8.2 months; 0.50, 0.36-0.70; p<0.0001). Likewise, for this patient population, progression-free survival was significantly longer with pembrolizumab 2 mg/kg than with docetaxel (median 5.0 months vs 4.1 months; HR 0.59, 95% CI 0.44-0.78; p=0.0001) and with pembrolizumab 10 mg/kg than with docetaxel (5.2 months vs 4.1 months; 0.59, 0.45-0.78; p<0.0001). Grade 3-5 treatment-related adverse events were less common with pembrolizumab than with docetaxel (43 [13%] of 339 patients given 2 mg/kg, 55 [16%] of 343 given 10 mg/kg, and 109 [35%] of 309 given docetaxel).<h4>Interpretation</h4>Pembrolizumab prolongs overall survival and has a favourable benefit-to-risk profile in patients with previously treated, PD-L1-positive, advanced non-small-cell lung cancer. These data establish pembrolizumab as a new treatment option for this population and validate the use of PD-L1 selection.<h4>Funding</h4>Merck & Co.","journal":"The Lancet","year":2016,"id":7253,"datarank":19.426629433101944,"base_score":8.779249716229046,"endowment":8.779249716229046,"self_citation_contribution":1.316887457434357,"citation_network_contribution":18.109741975667585,"self_endowment_contribution":1.316887457434357,"citer_contribution":18.109741975667585,"corpus_percentile":91.0,"corpus_rank":2099,"citation_count":6497,"citer_count":175,"citers_with_citation_signal":175,"citers_with_endowment":175,"datacite_reuse_total":0,"is_dataset":false,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2016-04-01","authors":[{"id":65214,"name":"Paul Baas","orcid":"0000-0001-7018-9556","position":1,"is_corresponding":false},{"id":65215,"name":"Dong-Wan Kim","orcid":null,"position":2,"is_corresponding":false},{"id":1544,"name":"Enriqueta Felip","orcid":"0000-0002-7620-0098","position":3,"is_corresponding":false},{"id":65216,"name":"José L Pérez-Gracia","orcid":null,"position":4,"is_corresponding":false},{"id":65217,"name":"Ji-Youn Han","orcid":null,"position":5,"is_corresponding":false},{"id":65218,"name":"Julian Molina","orcid":null,"position":6,"is_corresponding":false},{"id":65219,"name":"Joo-Hang Kim","orcid":"0000-0003-0408-8997","position":7,"is_corresponding":false},{"id":65220,"name":"Catherine Dubos Arvis","orcid":null,"position":8,"is_corresponding":false},{"id":65221,"name":"Myung-Ju Ahn","orcid":null,"position":9,"is_corresponding":false},{"id":65222,"name":"Margarita Majem","orcid":"0000-0002-9919-7485","position":10,"is_corresponding":false},{"id":65223,"name":"Mary J. Fidler","orcid":"0009-0004-9180-8626","position":11,"is_corresponding":false},{"id":65224,"name":"Gilberto de Castro","orcid":"0000-0001-8765-3044","position":12,"is_corresponding":false},{"id":65225,"name":"Marcelo Garrido","orcid":"0000-0001-8905-8986","position":13,"is_corresponding":false},{"id":65226,"name":"Gregory M. Lubiniecki","orcid":null,"position":14,"is_corresponding":false},{"id":65227,"name":"Yue Shentu","orcid":"0000-0002-9547-1387","position":15,"is_corresponding":false},{"id":65228,"name":"Ellie Im","orcid":null,"position":16,"is_corresponding":false},{"id":65229,"name":"Marisa Dolled-Filhart","orcid":null,"position":17,"is_corresponding":false},{"id":33768,"name":"Edward B. 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