Adjuvant Pembrolizumab for Patients With High-Risk Muscle-Invasive Urothelial Carcinoma

In the phase 3 AMBASSADOR trial, adjuvant pembrolizumab significantly improved the disease-free survival among patients with high-risk muscle-invasive urothelial carcinoma following radical surgery, when compared to observation.

There were 702 patients in this population who were randomized on a 1-to-1 basis to either receive 200 mg pembrolizumab every 3 weeks for 1 year (n = 354) or to undergo observation (n = 348). Randomization was stratified by pathological stage, centrally tested PD-L1 status, and previously neoadjuvant chemotherapy. The coprimary end points of this trial were disease-free survival (DFS) and overall survival (OS) in the intention-to-treat population.

At the time of the interim analysis, the median follow-up duration of 22.3 months for DFS and 36.9 months for OS. The median DFS was 29.0 months in the pembrolizumab arm vs 14.0 months in the observation arm (hazard ratio [HR], 0.69; P = .0013). The median OS was 50.9 months and 55.8 months, respectively (HR, 0.98; P = .88). Study authors noted that this end point “may have been impacted by [patients]s on the [observation] arm receiving a checkpoint inhibitor. At the time of the current report, the median duration of follow-up for DFS was 44.8 months. The median DFS was 29.6 months in the pembrolizumab arm vs 14.2 months in the observation arm. Grade ≥3 adverse events, regardless of attribution, were observed in 50.7% of patients with pembrolizumab and 31.6% of patients with observation. 

At the interim analysis, study authors concluded the results “support adjuvant pembro[lizumab] as a new therapeutic option for [patients] with [muscle-invasive urothelial carcinoma] with high risk for recurrence.”

Source:

Apolo AB, Ballman KV, Sonpavde G, et al. Adjuvant pembrolizumab versus observation in muscle-invasive urothelial carcinoma. N Eng J Med. Published online: September 14, 2024. doi: 10.1056/NEJMoa2401726

Apolo AB, Ballman KV, Sonpavde GP, et al. AMBASSADOR Alliance A031501: Phase III randomized adjuvant study of pembrolizumab in muscle-invasive and locally advanced urothelial carcinoma (MIUC) vs observation. J Clin Oncol. 2024;42(Number 4_suppl). doi: 10.1200/JSCO.2024.42.4_suppl.LBA531.