Dr Sonpavde on the AMBASSADOR Trial in Muscle-Invasive Urothelial Cancer

“These [data] are hypothesis generating. At the end of the day, adjuvant pembrolizumab, we think, could be added to the therapeutic armamentarium for the [treatment] of patients with high-risk muscle-invasive and locally advanced urothelial carcinoma.”

Guru P. Sonpavde, MD, medical director, Genitourinary (GU) Oncology, assistant director, Clinical Research Unit, Christopher K. Glanz Chair for Bladder Cancer Research, AdventHealth Cancer Institute, discusses the randomized phase 3 AMBASSADOR trial (NCT03244384) of pembrolizumab (Keytruda) in muscle-invasive and locally advanced urothelial carcinoma.

AMBASSADOR evaluated adjuvant pembrolizumab in patients with high-risk muscle-invasive urothelial carcinoma, Sonpavde begins, noting that this population included patients with bladder, upper tract, or urothelial carcinoma, predominantly of urothelial origin. Patients either underwent prior neoadjuvant chemotherapy or were cisplatin ineligible and did not receive cisplatin-based neoadjuvant therapy. The trial, which enrolled 702 patients, reported positive results at the 2024 Genitourinary Cancers Symposium, demonstrating an improvement in disease-free survival (DFS) with pembrolizumab vs observation, Sonpavde emphasizes. These findings were updated at the 2024 ESMO Congress, confirming that the DFS benefit persists with longer follow-up, he reports.

Although data regarding overall survival, a coprimary end point, are still immature, the DFS improvement is significant, consistent with earlier reports, Sonpavde continues. These data provide robust support for the role of pembrolizumab in the adjuvant setting for this high-risk population, according to Sonpavde. The positive results from the AMBASSADOR trial indicatethat pembrolizumab may also soon be available for the treatment of this patient population pending regulatory review, Sonpavde adds.

Interestingly, the trial indicated no significant trend for improved outcomes with pembrolizumab vs observation in PD-L1–high patients, although this was a secondary end point, he expands. Additionally, data hinted at better outcomes in patients with bladder cancer compared with those with upper tract disease, particularly involving the renal pelvis. Although these findings are hypothesis generating, they highlight potential areas for further exploration, Sonpavde states. Adjuvant pembrolizumab could significantly expand therapeutic options for patients with high-risk muscle-invasive urothelial carcinoma if approved for this population, he concludes.