• Luis Paz-Ares, Alexander Luft, David Vicente, Ali Tafreshi, Mahmut Gümüş, Julien Mazières, Barbara Hermes, Filiz Çay Şenler, Tibor Csőszi, Andrea Fülöp, Jerónimo Rodríguez-Cid, Jonathan Wilson, Shunichi Sugawara, Terufumi Kato, Ki Hyeong Lee, Ying Cheng, Silvia Novello, Balazs Halmos, Xiaodong Li, Gregory M Lubiniecki, Bilal Piperdi, Dariusz M Kowalski, and KEYNOTE-407 Investigators.
• From Hospital Universitario 12 de Octubre, Spanish National Cancer Research Center, Universidad Complutense and Ciberonc, Madrid (L.P.-A.), and Hospital Universitario Virgen Macarena, Seville (D.V.) - both in Spain; Leningrad Regional Clinical Hospital, St. Petersburg, Russia (A.L.); Wollongong Oncology and Wollongong Private Hospital, Wollongong, NSW, Australia (A.T.); Istanbul Medeniyet University Hospital, Istanbul (M.G.), and Ankara University, Ankara (F.Ç.Ş.) - both in Turkey; Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier, Toulouse, France (J.M.); Universitätsklinikum Tübingen, Tübingen, Germany (B. Hermes); Jász-Nagykun-Szolnok County Hospital, Szolnok (T.C.), and Országos Korányi TBC és Pulmonológiai Intézet, Budapest (A.F.) - both in Hungary; Oncology Center, Medica Sur Hospital, Mexico City (J.R.-C.); Humber River Regional Hospital, Toronto (J.W.); Sendai Kousei Hospital, Sendai (S.S.), and the Kanagawa Cancer Center, Yokohama (T.K.) - both in Japan; Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheong-ju, South Korea (K.H.L.); Jilin Cancer Hospital, Changchun, China (Y.C.); University of Turin, Orbassano, Italy (S.N.); Montefiore Medical Center-Albert Einstein College of Medicine, New York (B. Halmos); Merck, Kenilworth, NJ (X.L., G.M.L., B.P.); and the Maria Skłodowska-Curie Institute of Oncology, Warsaw, Poland (D.M.K.).
• N. Engl. J. Med. 2018 Nov 22; 379 (21): 2040-2051.

BackgroundStandard first-line therapy for metastatic, squamous non-small-cell lung cancer (NSCLC) is platinum-based chemotherapy or pembrolizumab (for patients with programmed death ligand 1 [PD-L1] expression on ≥50% of tumor cells). More recently, pembrolizumab plus chemotherapy was shown to significantly prolong overall survival among patients with nonsquamous NSCLC.MethodsIn this double-blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, 559 patients with untreated metastatic, squamous NSCLC to receive 200 mg of pembrolizumab or saline placebo for up to 35 cycles; all the patients also received carboplatin and either paclitaxel or nanoparticle albumin-bound [nab]-paclitaxel for the first 4 cycles. Primary end points were overall survival and progression-free survival.ResultsAfter a median follow-up of 7.8 months, the median overall survival was 15.9 months (95% confidence interval [CI], 13.2 to not reached) in the pembrolizumab-combination group and 11.3 months (95% CI, 9.5 to 14.8) in the placebo-combination group (hazard ratio for death, 0.64; 95% CI, 0.49 to 0.85; P<0.001). The overall survival benefit was consistent regardless of the level of PD-L1 expression. The median progression-free survival was 6.4 months (95% CI, 6.2 to 8.3) in the pembrolizumab-combination group and 4.8 months (95% CI, 4.3 to 5.7) in the placebo-combination group (hazard ratio for disease progression or death, 0.56; 95% CI, 0.45 to 0.70; P<0.001). Adverse events of grade 3 or higher occurred in 69.8% of the patients in the pembrolizumab-combination group and in 68.2% of the patients in the placebo-combination group. Discontinuation of treatment because of adverse events was more frequent in the pembrolizumab-combination group than in the placebo-combination group (13.3% vs. 6.4%).ConclusionsIn patients with previously untreated metastatic, squamous NSCLC, the addition of pembrolizumab to chemotherapy with carboplatin plus paclitaxel or nab-paclitaxel resulted in significantly longer overall survival and progression-free survival than chemotherapy alone. (Funded by Merck Sharp & Dohme; KEYNOTE-407 ClinicalTrials.gov number, NCT02775435 .).

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