Patients facing muscle-invasive urothelial cancer with a high risk of recurrence after surgery might have a promising new treatment option. The Phase III AMBASSADOR (A031501) trial, led by the Alliance for Clinical Trials in Oncology, has reported positive results for the adjuvant treatment of patients with localized muscle-invasive urothelial carcinoma (MIUC) and locally advanced urothelial carcinoma.
Presenting late-breaking data at the 2024 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Cancers Symposium, the trial focused on pembrolizumab, an anti-PD-1 therapy. In a pre-specified interim analysis review, pembrolizumab demonstrated a statistically significant and clinically meaningful improvement in disease-free survival (DFS) compared to observation in post-surgery patients, fulfilling one of the trial’s dual primary endpoints.
After a median follow-up of 22.3 months, pembrolizumab reduced the risk of DFS or death by 31% versus observation. The median DFS was 29.0 months for pembrolizumab, marking a 15-month improvement over observation. Notably, these DFS results were consistent regardless of patients’ PD-L1 expression status. While the other dual primary endpoint of overall survival (OS) did not reach statistical significance at the interim analysis, it will continue to be followed as data mature.
The trial enrolled 702 patients, and the safety profile of pembrolizumab remained consistent with previously reported studies. Grade 3+ adverse events occurred in 48.4% of patients receiving pembrolizumab versus 31.8% in the observation group. Withdrawals from the trial without events were 17.4% in the pembrolizumab group versus 27.2% in the observation arm. In the observation arm, 22% of patients subsequently received an immune checkpoint inhibitor.
Muscle-invasive bladder cancer, which affects the deep muscle of the bladder wall, often leads to recurrence despite surgery. The positive results from the AMBASSADOR trial suggest that pembrolizumab might provide an effective adjuvant treatment option for these patients, particularly in reducing the risk of disease recurrence and metastases. This development is considered a significant advancement in the bladder cancer community.