Luis Paz-Ares1, Alexander Luft1, David Vicente1, Ali Tafreshi1, Mahmut Gümüş1, Julien Mazières1, Barbara Hermes1, Filiz Çay Şenler1, Tibor Csőszi1, Andrea Fülöp1, Jerónimo Rodríguez-Cid1, Jonathan Wilson1, Shunichi Sugawara1, Terufumi Kato1, Ki Hyeong Lee1, Ying Cheng1, Silvia Novello1, Balazs Halmos1, Xiaodong Li1, Gregory M Lubiniecki1, Bilal Piperdi1, Dariusz M Kowalski1. 1. 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.).
Abstract
BACKGROUND:Standard 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. METHODS: In 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 ofpembrolizumab 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. RESULTS: After 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%). CONCLUSIONS: In 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 .).
RCT Entities:
BACKGROUND: Standard 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. METHODS: In 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. RESULTS: After 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%). CONCLUSIONS: In 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 .).
Authors: Sen Yang; Dongfang Tang; Yu C Zhao; Hongliang Liu; Sheng Luo; Thomas E Stinchcombe; Carolyn Glass; Li Su; Sipeng Shen; David C Christiani; Qiming Wang; Qingyi Wei Journal: Int J Cancer Date: 2019-12-19 Impact factor: 7.396
Authors: Salma K Jabbour; Abigail T Berman; Roy H Decker; Yong Lin; Steven J Feigenberg; Scott N Gettinger; Charu Aggarwal; Corey J Langer; Charles B Simone; Jeffrey D Bradley; Joseph Aisner; Jyoti Malhotra Journal: JAMA Oncol Date: 2020-06-01 Impact factor: 31.777
Authors: Charles M Rudin; Mark M Awad; Alejandro Navarro; Maya Gottfried; Solange Peters; Tibor Csőszi; Parneet K Cheema; Delvys Rodriguez-Abreu; Mirjana Wollner; James Chih-Hsin Yang; Julien Mazieres; Francisco J Orlandi; Alexander Luft; Mahmut Gümüş; Terufumi Kato; Gregory P Kalemkerian; Yiwen Luo; Victoria Ebiana; M Catherine Pietanza; Hye Ryun Kim Journal: J Clin Oncol Date: 2020-05-29 Impact factor: 44.544
Authors: Carminia M Della Corte; Triparna Sen; Carl M Gay; Kavya Ramkumar; Lixia Diao; Robert J Cardnell; Bertha Leticia Rodriguez; C Allison Stewart; Vassiliki A Papadimitrakopoulou; Laura Gibson; Jared J Fradette; Qi Wang; Youhong Fan; David H Peng; Marcelo V Negrao; Ignacio I Wistuba; Junya Fujimoto; Luisa M Solis Soto; Carmen Behrens; Ferdinandos Skoulidis; John V Heymach; Jing Wang; Don L Gibbons; Lauren A Byers Journal: J Thorac Oncol Date: 2020-02-15 Impact factor: 15.609