TY - JOUR
T1 - Adjuvant Pembrolizumab versus Observation in Muscle-Invasive Urothelial Carcinoma
AU - Apolo, Andrea B
AU - Ballman, Karla V
AU - Sonpavde, Guru
AU - Berg, Stephanie
AU - Kim, William Y
AU - Parikh, Rahul
AU - Teo, Min Yuen
AU - Sweis, Randy F
AU - Geynisman, Daniel M
AU - Grivas, Petros
AU - Chatta, Gurkamal
AU - Reichert, Zachery Roger
AU - Kim, Joseph W
AU - Bilen, Mehmet Asim
AU - McGregor, Bradley
AU - Singh, Parminder
AU - Tripathi, Abhishek
AU - Cole, Suzanne
AU - Simon, Nicholas
AU - Niglio, Scot
AU - Ley, Lisa
AU - Cordes, Lisa
AU - Srinivas, Sandy
AU - Huang, Jiaoti
AU - Odegaard, Meagan
AU - Watt, Colleen
AU - Petrylak, Daniel
AU - Hoffman-Censits, Jeannie
AU - Wen, Yujia
AU - Hahn, Olwen
AU - Mitchell, Cecilia
AU - Tan, Alan
AU - Streicher, Howard
AU - Sharon, Elad
AU - Moon, Helen
AU - Woods, Michael
AU - Halabi, Susan
AU - Perez Burbano, Gabriela
AU - Morris, Michael J
AU - Rosenberg, Jonathan E
N1 - Copyright © 2024 Massachusetts Medical Society.
PY - 2024/9/15
Y1 - 2024/9/15
N2 - 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.).
AB - 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.).
KW - Aged
KW - Aged, 80 and over
KW - Antibodies, Monoclonal, Humanized/therapeutic use
KW - Antineoplastic Agents, Immunological/therapeutic use
KW - Carcinoma, Transitional Cell/drug therapy
KW - Chemotherapy, Adjuvant
KW - Disease-Free Survival
KW - Female
KW - Humans
KW - Intention to Treat Analysis
KW - Kaplan-Meier Estimate
KW - Male
KW - Middle Aged
KW - Neoplasm Invasiveness
KW - Survival Analysis
KW - Urinary Bladder Neoplasms/drug therapy
KW - Urologic Neoplasms/drug therapy
KW - Watchful Waiting
U2 - 10.1056/NEJMoa2401726
DO - 10.1056/NEJMoa2401726
M3 - Article
C2 - 39282902
SN - 0028-4793
VL - 392
SP - 45
EP - 55
JO - New England Journal of Medicine
JF - New England Journal of Medicine
ER -
