biostudies-literatureApolo ABIntramural NIH HHSNCATS NIH HHSNCI NIH HHSNational Cancer Institute Intramural ProgramCancer Therapy Evaluation ProgramNational Cancer Institute of the National Institutes of HealthMerckCenter for Cancer Research45-55https://www.ebi.ac.uk/biostudies/studies/S-EPMC11698643biostudies-literatureUnknown392(1)<h4>Background</h4>Muscle-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.<h4>Methods</h4>In 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.<h4>Results</h4>A 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 50.6% of the patients in the pembrolizumab group and in 31.6% of the patients in the observation group.<h4>Conclusions</h4>Among 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.).The New England journal of medicineAdjuvant Pembrolizumab versus Observation in Muscle-Invasive Urothelial Carcinoma.PMC11698643UG1 CA233247UG1 CA233302UG1CA233337U10CA180882P30 CA008748UG1 CA233327U10CA180868 (NRG)UL1 TR001863UG1 CA233290UG1 CA233191UG1CA233160UG1CA233180UG1 CA233196UG1 CA233193UG1 CA233270NCI ZIA BC 011351UG1CA239767UG1 CA232760UG1 CA233373UG1 CA233253UG1CA233327UG1CA233247UG1CA233302UG1 CA233337U10 CA180882ZIA BC011351UG1 CA233180U10 CA180820UG1CA233193UG1CA233270UG1CA233191UG1CA233290UG1CA233253U10 CA180868UG1CA233373UG1 CA239767UG1 CA233160UG1CA233196U10 CA180821U10 CA180888U10CA180820 (ECOG-ACRIN)UG1CA232760U10CA180888U10CA180821Wen YWoods MSimon NHuang JKim WYGrivas PParikh RWatt CReichert ZRMorris MJBallman KVTeo MYChatta GSingh PTripathi ACole SSrinivas SPerez Burbano GSharon EGeynisman DMCordes LRosenberg JEOdegaard MMcGregor BNiglio SHalabi SHahn OApolo ABKim JWStreicher HBerg SBilen MAPetrylak DTan ASonpavde GHoffman-Censits JLey LSweis RFMitchell CMoon HfalseAdjuvant Pembrolizumab versus Observation in Muscle-Invasive Urothelial Carcinoma.<h4>Background</h4>Muscle-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.<h4>Methods</h4>In 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.<h4>Results</h4>A 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 50.6% of the patients in the pembrolizumab group and in 31.6% of the patients in the observation group.<h4>Conclusions</h4>Among 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.).2025-01-01T00:00:00Z2025 Jan2026-06-01T23:13:03.156Z2026-05-23T03:08:06.552ZS-EPMC116986433928290210.1056/NEJMoa2401726