• Nicoletta Colombo, Coraline Dubot, Domenica Lorusso, M Valeria Caceres, Kosei Hasegawa, Ronnie Shapira-Frommer, Krishnansu S Tewari, Pamela Salman, Edwin Hoyos Usta, Eduardo Yañez, Mahmut Gümüş, Mivael Olivera Hurtado de Mendoza, Vanessa Samouëlian, Vincent Castonguay, Alexander Arkhipov, Sarper Toker, Kan Li, Stephen M Keefe, Bradley J Monk, and KEYNOTE-826 Investigators.
• From the University of Milan-Bicocca and European Institute of Oncology IRCCS, Milan (N.C.), and Fondazione Policlinico Universitario A. Gemelli IRCCS and Catholic University of the Sacred Heart, Rome (D.L.) - both in Italy; Institut Curie Saint-Cloud, Group d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens, Saint-Cloud, France (C.D.); Instituto de Oncología Ángel H. Roffo, Buenos Aires (M.V.C.); Saitama Medical University International Medical Center, Hidaka, Japan (K.H.); Ella Lemelbaum Institute for Immuno-Oncology, Sheba Medical Center, Ramat Gan, Israel (R.S.-F.); the University of California, Irvine, Orange (K.S.T.); Oncovida Cancer Center, Providencia (P.S.), and Universidad de la Frontera, Temuco (E.Y.) - both in Chile; IMAT (Instituto Médico de Alta Tecnología) Oncomedica, Monteria, Colombia (E.H.U.); Istanbul Medeniyet University Hospital, Istanbul, Turkey (M.G.); Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru (M.O.H.M.); Centre Hospitalier de l'Université de Montréal, Centre de Recherche de l'Université de Montréal, Université de Montréal, Montreal (V.S.), and Centre Hospitalier Universitaire de Québec, Université Laval, Quebec (V.C.) - both in Quebec, Canada; the Medical Rehabilitation Center of the Ministry of Health of the Russian Federation, Moscow (A.A.); Merck, Kenilworth, NJ (S.T., K.L., S.M.K.); and Arizona Oncology (U.S. Oncology Network), University of Arizona College of Medicine, Creighton University School of Medicine, Phoenix (B.J.M.).
• N. Engl. J. Med. 2021 Nov 11; 385 (20): 185618671856-1867.

BackgroundPembrolizumab has efficacy in programmed death ligand 1 (PD-L1)-positive metastatic or unresectable cervical cancer that has progressed during chemotherapy. We assessed the relative benefit of adding pembrolizumab to chemotherapy with or without bevacizumab.MethodsIn a double-blind, phase 3 trial, we randomly assigned patients with persistent, recurrent, or metastatic cervical cancer in a 1:1 ratio to receive pembrolizumab (200 mg) or placebo every 3 weeks for up to 35 cycles plus platinum-based chemotherapy and, per investigator discretion, bevacizumab. The dual primary end points were progression-free survival and overall survival, each tested sequentially in patients with a PD-L1 combined positive score of 1 or more, in the intention-to-treat population, and in patients with a PD-L1 combined positive score of 10 or more. The combined positive score is defined as the number of PD-L1-staining cells divided by the total number of viable tumor cells, multiplied by 100. All results are from the protocol-specified first interim analysis.ResultsIn 548 patients with a PD-L1 combined positive score of 1 or more, median progression-free survival was 10.4 months in the pembrolizumab group and 8.2 months in the placebo group (hazard ratio for disease progression or death, 0.62; 95% confidence interval [CI], 0.50 to 0.77; P<0.001). In 617 patients in the intention-to-treat population, progression-free survival was 10.4 months and 8.2 months, respectively (hazard ratio, 0.65; 95% CI, 0.53 to 0.79; P<0.001). In 317 patients with a PD-L1 combined positive score of 10 or more, progression-free survival was 10.4 months and 8.1 months, respectively (hazard ratio, 0.58; 95% CI, 0.44 to 0.77; P<0.001). Overall survival at 24 months was 53.0% in the pembrolizumab group and 41.7% in the placebo group (hazard ratio for death, 0.64; 95% CI, 0.50 to 0.81; P<0.001), 50.4% and 40.4% (hazard ratio, 0.67; 95% CI, 0.54 to 0.84; P<0.001), and 54.4% and 44.6% (hazard ratio, 0.61; 95% CI, 0.44 to 0.84; P = 0.001), respectively. The most common grade 3 to 5 adverse events were anemia (30.3% in the pembrolizumab group and 26.9% in the placebo group) and neutropenia (12.4% and 9.7%, respectively).ConclusionsProgression-free and overall survival were significantly longer with pembrolizumab than with placebo among patients with persistent, recurrent, or metastatic cervical cancer who were also receiving chemotherapy with or without bevacizumab. (Funded by Merck Sharp and Dohme; KEYNOTE-826 ClinicalTrials.gov number, NCT03635567.).Copyright © 2021 Massachusetts Medical Society.

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