2024-01-27 13:07:02
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 today announced positive results from the phase III AMBASSADOR trial (A031501) for the adjuvant treatment of patients with locally advanced muscle invasive carcinoma (MIUC) and locally advanced urothelial carcinoma. Late data from the trial are being presented during an oral abstract session at the 2024 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Cancer Symposium (abstract no. LBA531) today.
Patients with muscle-invasive bladder cancer after radical surgery are at high risk of disease recurrence and metastasis. Pembrolizumab versus observation significantly reduced the risk of disease recurrence for these patients. These are data that we have been waiting a long time for in the bladder cancer community.”
Andrea B. Apollo, MD, Study Chair for the AMBASSADOR Trial and Chief of the Bladder Cancer Section of the Genitourinary Malignancies Branch and Director of the Multidisciplinary Clinic for Bladder Cancer and Genitourinary Tumors at the National Cancer Institute’s Cancer Research Center
In a prespecified interim analysis review, the anti-PD-1 therapy pembrolizumab showed a statistically significant and clinically meaningful improvement in disease-free survival (DFS) versus observation in postoperative patients, meeting 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% (HR=0.69 (95% CI, 0.55-0.87; p=0.0013) compared with observation in postoperative patients. Median DFS was 29.0 months (95% CI, 21.8-not estimable (NE)) for pembrolizumab and 14.0 months (95% CI, 9.7-20.2) for observation, a 15-month improvement. These DFS results were consistent regardless of PD-L1 expression status The trial’s other co-primary endpoint of overall survival (OS) did not reach statistical significance at the time of this interim analysis and will continue to be followed as the data mature (HR=0.98 (95% CI, 0.76-1.26); p=0.88). At a follow-up of 36.9 months, median OS was 50.9 months (95% CI, 43.9-NE) for pembrolizumab versus 55.8 months (95% CI, 53.3-NE) for observation (HR=0.98 (95% CI, 0.76) -1.26); p = 0.88).
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+ side effects (serious or medically significant side effects but not immediately life-threatening) occurred in 48.4% of patients who received pembrolizumab compared to 31.8% of patients in follow-up.
17.4% of the patients who received pembrolizumab withdrew from the trial without incident, compared to 27.2% of the observation arm. Seventy-six patients (22%) in the observation arm subsequently received an immune checkpoint inhibitor.
AMBASSADOR (A031501) is an open-label randomized phase III trial evaluating pembrolizumab versus observation for the adjuvant treatment of locally advanced MIUC and locally advanced urothelial carcinoma. The co-primary endpoints are OS and DFS, and the secondary endpoints include OS and DFS in PD-L1 positive and negative patients. The trial included 702 patients who were randomly assigned to receive pembrolizumab (200 mg intravenously every three weeks for up to 18 cycles) or to undergo observation.
It is estimated that approximately 82,290 people in the United States will be diagnosed with bladder cancer in 2023. Worldwide, there were approximately 573,000 new cases and 212,000 deaths from bladder cancer in 2020. Muscle-invasive bladder cancer is a cancer Bladder that has spread deep into the muscle of the bladder wall, and locally advanced urothelial cancer is cancer that starts in the urothelial cells and has spread from where it started to nearby tissue or lymph nodes. Despite surgery, up to 50% of patients with bladder cancer experience a recurrence within 12 months .
AMBASSADOR is funded by the National Cancer Institute (NCI), part of the National Institutes of Health, and is led and managed by the NCI-funded Alliance for Clinical Trials in Oncology with the participation of the NCI-funded National Clinical Trials Network (NCTN). Part of Merck’s collaboration with NCI through a Cooperative Research and Development Agreement (CRADA). For more information about the AMBASSADOR trial, visit ClinicalTrials.gov.
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