• Michiel S van der Heijden, Guru Sonpavde, Thomas Powles, Andrea Necchi, Mauricio Burotto, Michael Schenker, Juan Pablo Sade, Aristotelis Bamias, Philippe Beuzeboc, Jens Bedke, Jan Oldenburg, Gurkamal Chatta, Yüksel Ürün, Dingwei Ye, Zhisong He, Begoña P Valderrama, Ja Hyeon Ku, Yoshihiko Tomita, Jeiry Filian, Lily Wang, Daniela Purcea, Miraj Y Patel, Federico Nasroulah, Matthew D Galsky, and CheckMate 901 Trial Investigators.
• From the Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam (M.S.H.); Medical Oncology, Genitourinary Section, Dana-Farber Cancer Institute, Harvard Medical School, Boston (G.S.); the Department of Genitourinary Oncology, Barts Cancer Institute, Queen Mary University of London, London (T.P.); the Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (A.N.); the Department of Oncology, Bradford Hill Clinical Research Center, Santiago, Chile (M.B.); the Department of Medical Oncology, Sf. Nectarie Oncology Center, Department of Oncology, University of Medicine and Pharmacy, Craiova, Romania (M.S.); the Department of Clinical Oncology, Alexander Fleming Institute, Buenos Aires (J.P.S.); the Second Propedeutic Department of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, Athens (A.B.); the Department of Urologic Oncology, Hopital Foch, Suresnes, France (P.B.); the Department of Urology, Eberhard Karls University Tübingen, Tübingen, Germany (J.B.); the Department of Oncology, Akershus University Hospital, Lørenskog, Norway (J.O.); Roswell Park Comprehensive Cancer Center, Buffalo (G.C.), and the Department of Medicine, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York (M.D.G.) - both in New York; the Department of Medical Oncology, Ankara University, Ankara, Turkey (Y.Ü.); the Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai (D.Y.), and the Department of Urology, Peking University First Hospital, Beijing (Z.H.) - both in China; the Department of Medical Oncology, Hospital Universitario Virgen del Rocío, Sevilla, Spain (B.P.V.); Seoul National University Hospital, Seoul, South Korea (J.H.K.); the Department of Urology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan (Y.T.); Bristol Myers Squibb, Princeton, NJ (J.F., L.W., M.Y.P., F.N.); and Bristol Myers Squibb, Boudry, Switzerland (D.P.).
• N. Engl. J. Med. 2023 Nov 9; 389 (19): 177817891778-1789.

BackgroundNo new agent has improved overall survival in patients with unresectable or metastatic urothelial carcinoma when added to first-line cisplatin-based chemotherapy.MethodsIn this phase 3, multinational, open-label trial, we randomly assigned patients with previously untreated unresectable or metastatic urothelial carcinoma either to receive intravenous nivolumab (at a dose of 360 mg) plus gemcitabine-cisplatin (nivolumab combination) every 3 weeks for up to six cycles, followed by nivolumab (at a dose of 480 mg) every 4 weeks for a maximum of 2 years, or to receive gemcitabine-cisplatin alone every 3 weeks for up to six cycles. The primary outcomes were overall and progression-free survival. The objective response and safety were exploratory outcomes.ResultsA total of 608 patients underwent randomization (304 to each group). At a median follow-up of 33.6 months, overall survival was longer with nivolumab-combination therapy than with gemcitabine-cisplatin alone (hazard ratio for death, 0.78; 95% confidence interval [CI], 0.63 to 0.96; P = 0.02); the median survival was 21.7 months (95% CI, 18.6 to 26.4) as compared with 18.9 months (95% CI, 14.7 to 22.4), respectively. Progression-free survival was also longer with nivolumab-combination therapy than with gemcitabine-cisplatin alone (hazard ratio for progression or death, 0.72; 95% CI, 0.59 to 0.88; P = 0.001). The median progression-free survival was 7.9 months and 7.6 months, respectively. At 12 months, progression-free survival was 34.2% and 21.8%, respectively. The overall objective response was 57.6% (complete response, 21.7%) with nivolumab-combination therapy and 43.1% (complete response, 11.8%) with gemcitabine-cisplatin alone. The median duration of complete response was 37.1 months with nivolumab-combination therapy and 13.2 months with gemcitabine-cisplatin alone. Grade 3 or higher adverse events occurred in 61.8% and 51.7% of the patients, respectively.ConclusionsCombination therapy with nivolumab plus gemcitabine-cisplatin resulted in significantly better outcomes in patients with previously untreated advanced urothelial carcinoma than gemcitabine-cisplatin alone. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 901 ClinicalTrials.gov number, NCT03036098.).Copyright © 2023 Massachusetts Medical Society.

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