Patients with muscle-invasive urothelial cancer and a high risk of recurrence after surgery may have a new treatment option. The Alliance for Clinical Trials in Oncology announced positive results from the phase III AMBASSADOR (A031501) trial for the adjuvant treatment of patients with localized muscle-invasive urothelial carcinoma and locally advanced urothelial carcinoma. Late-breaking data from the trial were presented by Andrea Apolo, MD, and colleagues at the 2024 ASCO Genitourinary Cancers Symposium (Abstract LBA531).
“Patients with muscle-invasive bladder cancer after radical surgery are at high risk of disease recurrence and metastases. Pembrolizumab vs observation significantly reduced the risk of disease recurrence for these patients,” said Dr. Apolo, study chair for the AMBASSADOR trial, Head of the Bladder Cancer Section of the Genitourinary Malignancies Branch, and Director of the Bladder Cancer and Genitourinary Tumors Multidisciplinary Clinic at the Center for Cancer Research of the National Cancer Institute. “[These are] long-awaited data in the bladder cancer community.”
Andrea Apolo, MD
It is estimated that approximately 82,290 people in the United States were diagnosed with bladder cancer in 2023. Globally, there were approximately 573,000 new cases and 212,000 deaths from bladder cancer in 2020. Despite surgery, up to 50% of patients with bladder cancer experience disease recurrence within 12 months.
AMBASSADOR (A031501) is a randomized, open-label phase III trial evaluating pembrolizumab vs observation for the adjuvant treatment of localized muscle-invasive urothelial carcinoma and locally advanced urothelial carcinoma. The dual primary endpoints are overall survival and disease-free survival, and secondary endpoints include overall survival and disease-free survival in PD-L1−positive and −negative patients. The trial enrolled 702 patients who were randomly assigned to receive pembrolizumab at 200 mg intravenously every 3 weeks for up to 18 cycles or undergo observation.
Key Findings
At a prespecified interim analysis review, pembrolizumab, an anti–PD-1 therapy, demonstrated a statistically significant and clinically meaningful improvement in disease-free survival vs observation in patients after surgery, meeting one of the trial’s dual primary endpoints. After a median follow-up of 22.3 months, pembrolizumab reduced the risk of disease-free survival or death by 31% (hazard ratio [HR] = 0.69, 95% confidence interval [CI] = 0.55–0.87, P = .0013) vs observation in patients after surgery. Median disease-free survival was 29.0 months (95% CI = 21.8 months to not evaluable) for pembrolizumab and 14.0 months (95% CI = 9.7–20.2 months) for observation—an improvement of 15 months. These disease-free survival results were consistent regardless of patients’ PD-L1 expression status.
The trial’s other dual primary endpoint of overall survival did not reach statistical significance at the time of this interim analysis and will continue to be followed as data mature (HR = 0.98, 95% CI = 0.76–1.26, P = .88). After a median follow-up of 36.9 months, median overall survival was 50.9 months (95% CI = 43.9 months to not evaluable) for pembrolizumab vs 55.8 months (95% CI = 53.3 months to not evaluable) for observation (HR = 0.98, 95% CI = 0.76–1.26, P = .88).
Safety
The safety profile of pembrolizumab in this trial was consistent with that observed in previously reported studies, and no new safety signals were identified. Grade ≥ 3 adverse events occurred in 48.4% of patients receiving pembrolizumab vs 31.8% of patients under observation.
About 17% of patients receiving pembrolizumab withdrew from the trial without event vs 27.2% from the observation arm. Seventy-six patients (22%) in the observation arm subsequently received an immune checkpoint inhibitor.
Disclosure: AMBASSADOR is sponsored by the National Cancer Institute (NCI) and is being led and conducted by the NCI-funded Alliance for Clinical Trials in Oncology with participation from the NCI-funded national clinical trials network (NCTN) as part of Merck’s collaboration with the NCI through a Cooperative Research and Development Agreement (CRADA).
