According to interim DFS/OS results from the phase 3 AMBASSADOR Alliance AO31501 study, adjuvant pembrolizumab provided statistically significant and clinically meaningful disease-free survival (DFS) improvement to patients with high-risk muscle-invasive urothelial carcinoma after surgical resection.

These results were presented by Andrea B. Apolo, MD, National Cancer Institute, Bethesda, Maryland, and coauthors at the 2024 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium in San Francisco, California.

“Neoadjuvant platinum-based chemotherapy is the standard of care in patients who are cisplatin-eligible [however] many [patients] are [cisplatin]-ineligible or have persistent muscle-invasive disease after [neoadjuvant platinum-based chemotherapy] and surgery,” stated Dr Apollo and coauthors. Here, “we evaluated pembrolizumab as adjuvant therapy in [patients] with high-risk [muscle-invasive urothelial carcinoma] following surgical resection.”

In this open-label trial, 702 patients with histologically confirmed muscle-invasive urothelial carcinoma of the bladder, upper tract, or urethra who had ≥ pT2 and/or pN+ margins+ at surgical resection following neoadjuvant chemotherapy, ≥ pT3 and/or pN+ or margins+ at surgery without neoadjuvant chemotherapy, and were either cisplatin-ineligible or declined adjuvant cisplatin-based therapy were randomized on a 1-to-1 basis ≥4 to 16 weeks after surgical resection to receive 200 mg of pembrolizumab every 3 weeks (n = 354) for 1 year observation (n = 348). Randomization was stratified based on pathologic state, centrally tested PD-L1 status, and prior neoadjuvant chemotherapy. Enrollment was closed early due to the FDA approval of nivolumab for this population. The dual primary end points were DFS and overall survival (OS).

The median follow-up duration was 22.3 months for DFS and 36.9 months for OS, 3% of patients in the pembrolizumab arm and 21.6% of patients in the observational arm discontinued treatment before a DFS/OS event occurred. The median DFS was 29 months in the pembrolizumab arm and 14 months in the observational arm (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.55 to 0.87; P = .0013). At interim analysis (n events = 257), median OS was 50.9 months in the pembrolizumab arm and 55.8 months in the observational arm (HR, 0.98; 95% CI, 0.76 to 1.26; P = .88). Grade ≥3 adverse events occurred in 48.4% of patients in the pembrolizumab arm and 31.8% of patients in the observational arm.

“These results support adjuvant [pembrolizumab] as a new therapeutic option for [patients] with [muscle-invasive urothelial carcinoma] with high risk for recurrence,” concluded Dr Apollo and coauthors. “Additional follow-up is ongoing for the final DFS/OS, PD-L1 subgroups, and ctDNA analyses.”

Source:

Apollo 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. Presented at the 2024 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium in San Francisco, California. Abstract LBA 531