Adjuvant Pembrolizumab versus Observation in Muscle-Invasive Urothelial Carcinoma

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.).