• Dean F Bajorin, J Alfred Witjes, Jürgen E Gschwend, Michael Schenker, Begoña P Valderrama, Yoshihiko Tomita, Aristotelis Bamias, Thierry Lebret, Shahrokh F Shariat, Se Hoon Park, Dingwei Ye, Mads Agerbaek, Deborah Enting, Ray McDermott, Pablo Gajate, Avivit Peer, Matthew I Milowsky, Alexander Nosov, João Neif Antonio, Krzysztof Tupikowski, Laurence Toms, Bruce S Fischer, Anila Qureshi, Sandra Collette, Keziban Unsal-Kacmaz, Edward Broughton, Dimitrios Zardavas, Henry B Koon, and Matthew D Galsky.
• From the Memorial Sloan Kettering Cancer Center (D.F.B), Weill Cornell Medical College (S.F.S.), and Icahn School of Medicine at Mount Sinai (M.D.G.) - all in New York; Radboud University, Nijmegen, the Netherlands (J.A.W.); the Department of Urology, Technical University Munich, Munich, Germany (J.E.G.); Nectarie Oncology Center, Craiova, Romania (M.S.); Hospital Universitario Virgen del Rocío, Seville (B.P.V.), and Ramon y Cajal University Hospital, Madrid (P.G.) - both in Spain; Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan (Y.T.); National and Kapodistrian University of Athens, Athens (A.B.); the Urology Department, Hôpital Foch, Université Paris-Saclay, Université Versailles Saint-Quentin-en-Yvelines, Versailles, France (T.L.); Medical University of Vienna, Vienna General Hospital, Vienna (S.F.S.); University of Texas Southwestern Medical Center, Dallas (S.F.S.); Charles University, Prague, Czech Republic (S.F.S.); the Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow (S.F.S.), and Federal State Budget Institution N.N. Petrov National Medical Research Center of Oncology of the Ministry of Health Care of the Russian Federation, St. Petersburg (A.N.) - both in Russia; Sungkyunkwan University Samsung Medical Center, Seoul, South Korea (S.H.P.); Fudan University Shanghai Cancer Center, Shanghai, China (D.Y.); Aarhus University Hospital, Aarhus, Denmark (M.A.); Guy's and St. Thomas' NHS Foundation Trust, London (D.E.); St. Vincent's University Hospital and Cancer Trials Ireland, Dublin (R.M.); Rambam Health Care Campus, Haifa, Israel (A.P.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (M.I.M.); Hospital de Amor de Barretos-Pio XII Foundation, Barretos, Brazil (J.N.A.); the Subdivision of Urology, Wroclaw Comprehensive Cancer Center, Wroclaw, Poland (K.T.); and Bristol Myers Squibb, Princeton, NJ (L.T., B.S.F., A.Q., S.C., K.U.-K., E.B., D.Z., H.B.K.).
• N. Engl. J. Med. 2021 Jun 3; 384 (22): 210221142102-2114.

BackgroundThe role of adjuvant treatment in high-risk muscle-invasive urothelial carcinoma after radical surgery is not clear.MethodsIn a phase 3, multicenter, double-blind, randomized, controlled trial, we assigned patients with muscle-invasive urothelial carcinoma who had undergone radical surgery to receive, in a 1:1 ratio, either nivolumab (240 mg intravenously) or placebo every 2 weeks for up to 1 year. Neoadjuvant cisplatin-based chemotherapy before trial entry was allowed. The primary end points were disease-free survival among all the patients (intention-to-treat population) and among patients with a tumor programmed death ligand 1 (PD-L1) expression level of 1% or more. Survival free from recurrence outside the urothelial tract was a secondary end point.ResultsA total of 353 patients were assigned to receive nivolumab and 356 to receive placebo. The median disease-free survival in the intention-to-treat population was 20.8 months (95% confidence interval [CI], 16.5 to 27.6) with nivolumab and 10.8 months (95% CI, 8.3 to 13.9) with placebo. The percentage of patients who were alive and disease-free at 6 months was 74.9% with nivolumab and 60.3% with placebo (hazard ratio for disease recurrence or death, 0.70; 98.22% CI, 0.55 to 0.90; P<0.001). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 74.5% and 55.7%, respectively (hazard ratio, 0.55; 98.72% CI, 0.35 to 0.85; P<0.001). The median survival free from recurrence outside the urothelial tract in the intention-to-treat population was 22.9 months (95% CI, 19.2 to 33.4) with nivolumab and 13.7 months (95% CI, 8.4 to 20.3) with placebo. The percentage of patients who were alive and free from recurrence outside the urothelial tract at 6 months was 77.0% with nivolumab and 62.7% with placebo (hazard ratio for recurrence outside the urothelial tract or death, 0.72; 95% CI, 0.59 to 0.89). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 75.3% and 56.7%, respectively (hazard ratio, 0.55; 95% CI, 0.39 to 0.79). Treatment-related adverse events of grade 3 or higher occurred in 17.9% of the nivolumab group and 7.2% of the placebo group. Two treatment-related deaths due to pneumonitis were noted in the nivolumab group.ConclusionsIn this trial involving patients with high-risk muscle-invasive urothelial carcinoma who had undergone radical surgery, disease-free survival was longer with adjuvant nivolumab than with placebo in the intention-to-treat population and among patients with a PD-L1 expression level of 1% or more. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 274 ClinicalTrials.gov number, NCT02632409.).Copyright © 2021 Massachusetts Medical Society.

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