• Andrea B Apolo, Karla V Ballman, Guru Sonpavde, Stephanie Berg, William Y Kim, Rahul Parikh, Min Yuen Teo, Randy F Sweis, Daniel M Geynisman, Petros Grivas, Gurkamal Chatta, Zachery Roger Reichert, Joseph W Kim, Mehmet Asim Bilen, Bradley McGregor, Parminder Singh, Abhishek Tripathi, Suzanne Cole, Nicholas Simon, Scot Niglio, Lisa Ley, Lisa Cordes, Sandy Srinivas, Jiaoti Huang, Meagan Odegaard, Colleen Watt, Daniel Petrylak, Jeannie Hoffman-Censits, Yujia Wen, Olwen Hahn, Cecilia Mitchell, Alan Tan, Howard Streicher, Elad Sharon, Helen Moon, Michael Woods, Susan Halabi, Gabriela Perez Burbano, Michael J Morris, and Jonathan E Rosenberg.
• From the Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda (A.B.A., N.S., S.N., L.L., L.C.), the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.H.-C.), and the Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Rockville (H.S., E.S.) - all in Maryland; the Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN (K.V.B., M.O., C.M., G.P.B.); AdventHealth Cancer Institute and the University of Central Florida, Orlando (G.S.); Dana-Farber/Harvard Cancer Center, Boston (S.B., B.M.); UNC Lineberger Comprehensive Cancer Center, Chapel Hill (W.Y.K.), and Duke University Medical Center and Duke Cancer Institute, Durham (J.H., S.H.) - both in North Carolina; the University of Kansas Cancer Center, Westwood (R.P.); Memorial Sloan Kettering Cancer Center, New York (M.Y.T., M.J.M., J.E.R.), and Roswell Park Comprehensive Cancer Center, Buffalo (G.C.) - both in New York; the University of Chicago Comprehensive Cancer Center, Chicago (R.F.S., C.W., Y.W., O.H.), and Loyola University Medical Center, Maywood (M.W.) - both in Illinois; the Alliance Protocol Operations Office, University of Chicago, Chicago (C.W., Y.W., O.H.); Fox Chase Cancer Center, Philadelphia (D.M.G.); Fred Hutchinson Cancer Center and the University of Washington, Seattle (P.G.); Rogel Cancer Center, University of Michigan, Ann Arbor (Z.R.R.); Yale Cancer Center, Yale School of Medicine, New Haven, CT (J.W.K., D.P.); Winship Cancer Institute, Emory University, Atlanta (M.A.B.); Mayo Clinic Comprehensive Cancer Center, Phoenix, AZ (P.S.); Oklahoma University Health Stephenson Cancer Center, Oklahoma City (A. Tripathi); University of Texas Southwestern Medical Center, Dallas (S.C.); Stanford University, Stanford (S.S.), and Kaiser Permanente Riverside Medical Center, Riverside (H.M.) - both in California; and Vanderbilt-Ingram Cancer Center, Nashville (A. Tan).
• N. Engl. J. Med. 2024 Sep 15.

BackgroundMuscle-invasive urothelial carcinoma is an aggressive disease with high rates of relapse. Whether pembrolizumab as adjuvant therapy would be effective in patients with high-risk muscle-invasive urothelial carcinoma after radical surgery is unknown.MethodsIn this phase 3 trial, we randomly assigned patients, in a 1:1 ratio, to receive pembrolizumab at a dose of 200 mg every 3 weeks for 1 year or to undergo observation. Randomization was stratified according to pathological stage, centrally tested programmed death ligand 1 (PD-L1) status, and previous neoadjuvant chemotherapy. The coprimary end points were disease-free survival and overall survival in the intention-to-treat population. We considered the trial to be successful if either disease-free survival or overall survival was significantly longer with pembrolizumab than with observation.ResultsA total of 702 patients underwent randomization; 354 were assigned to receive pembrolizumab, and 348 were assigned to observation. As of July 5, 2024, the median duration of follow-up for disease-free survival was 44.8 months. The median disease-free survival was 29.6 months (95% confidence interval [CI], 20.0 to 40.7) with pembrolizumab and 14.2 months (95% CI, 11.0 to 20.2) with observation (hazard ratio for disease progression or death, 0.73; 95% CI, 0.59 to 0.90; two-sided P = 0.003). Grade 3 or higher adverse events (regardless of attribution) occurred in 50.7% of the patients in the pembrolizumab group and in 31.6% of the patients in the observation group.ConclusionsAmong patients with high-risk muscle-invasive urothelial carcinoma after radical surgery, disease-free survival was significantly longer with adjuvant pembrolizumab than with observation. (Funded by the National Cancer Institute of the National Institutes of Health and others; Alliance A031501 AMBASSADOR ClinicalTrials.gov number, NCT03244384.).Copyright © 2024 Massachusetts Medical Society.

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