The Alliance Data and Safety Monitoring Board has determined that adjuvant pembrolizumab may improve disease-free survival in patients with localized muscle-invasive urothelial carcinoma and locally advanced urothelial carcinoma, according to the Alliance for Clinical Trials in Oncology.
Background
Globally, there were approximately 573,000 new cases and 212,000 deaths from bladder cancer in 2020. It has been estimated that 82,290 U.S. patients will receive a diagnosis of bladder cancer in 2023.
Muscle-invasive urothelial carcinoma is a type of bladder cancer that has spread into the deep muscle of the bladder wall, and locally advanced urothelial carcinoma begins in the urothelial cells and metastasizes to nearby tissue or lymph nodes. Despite surgery, up to 50% of patients with urothelial carcinoma may experience recurrence within 12 months.
"The AMBASSADOR trial provides critically important data to contextualize the role of adjuvant immune checkpoint blockade in the treatment of patients with muscle-invasive urothelial [carcinoma], once again demonstrating the clinical and scientific impact of the National Cancer Institute's National Clinical Trials Network Treatment Studies," explained Matthew Galsky, MD, Professor of Medicine at the Icahn School of Medicine at Mount Sinai, Associate Director for Translational Research at The Tisch Cancer Institute, and Co-Chair of the Genitourinary Committee at the Alliance for Clinical Trials in Oncology.
Study Methods and Results
In the new open-label phase III AMBASSADOR trial (ClinicalTrials.gov identifier NCT03244384), researchers randomly assigned 702 patients with localized muscle-invasive urothelial carcinoma and locally advanced urothelial carcinoma to receive adjuvant treatment with either 200 mg of intravenous pembrolizumab every 3 weeks for up to 18 cycles or observation.
The dual primary endpoints of the trial were overall survival and disease-free survival. The secondary endpoints were overall survival and disease-free survival in patients with PD-L1–positive and –negative tumors.
In a prespecified interim analysis review, the researchers found that pembrolizumab demonstrated a statistically significant and clinically meaningful improvement in disease-free survival compared with observation following surgery.
The safety profile of pembrolizumab in this trial was consistent with that observed in previously reported studies, and the researchers identified no new safety signals.
Conclusions
“Cancer recurrence after surgery can be a devastating event for patients. In this study, pembrolizumab treatment led to a significant improvement in disease-free survival compared [with] observation, without any new safety signals,” highlighted Jonathan Rosenberg, MD, Chief of Genitourinary Oncology Service in the Division of Solid Tumor Oncology at Memorial Sloan Kettering Cancer Center and Co-Chair the Genitourinary Committee at the Alliance for Clinical Trials in Oncology. “These results will help us further understand the role of immune checkpoint blockade in this patient population,” he underscored. The researchers plan to continue evaluating its other dual primary endpoint of overall survival.
“Patients with muscle-invasive [urothelial carcinoma] 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,” emphasized study chair Andrea B. Apolo, MD, Head of the Bladder Cancer Section of the Genitourinary Malignancies Branch and Director of the Bladder Cancer and Genitourinary Tumors Multidisciplinary Clinic in the Center for Cancer Research at the National Cancer Institute. “This is long-awaited data in the bladder cancer community, and we are thrilled with the positive results of the AMBASSADOR [trial] and what this means for our patients with [urothelial carcinoma],” she concluded.
Disclosure: The AMBASSADOR trial is sponsored by the National Cancer Institute—and is being led and conducted by the Alliance for Clinical Trials in Oncology in participation with the National Clinical Trials Network as part of Merck’s collaboration with the National Cancer Institute through a Cooperative Research and Development Agreement.
