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Graphic illustration of a human urinary bladder in the background and cancer cells floating in and around the bladder.
Muscle-invasive bladder cancer spreads into the deep muscle of the bladder wall and may recur after surgery within 12 months.
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Pembrolizumab Shows Positive Results in Bladder Cancer Trial

Globally, there were around 573,000 new cases and 212,000 deaths from bladder cancer in 2020

The Alliance for Clinical Trials in Oncology
Published:Jan 26, 2024
|2 min read
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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 recently announced positive results from the Phase 3 AMBASSADOR (A031501) trial for the adjuvant treatment of patients with localized muscle-invasive urothelial carcinoma (MIUC) and locally advanced urothelial carcinoma. 

Muscle-invasive bladder cancer is bladder cancer that has spread into the deep muscle of the bladder wall, and locally advanced urothelial cancer is cancer that begins in the urothelial cells and has spread from where it started to nearby tissue or lymph nodes. Despite surgery, up to 50 percent of patients with bladder cancer experience recurrence within 12 months.


“Patients with muscle-invasive bladder cancer after radical surgery are at high risk of disease recurrence and metastases. Pembrolizumab versus observation significantly reduced the risk of disease recurrence for these patients,” said Andrea B. Apolo, MD, study chair for the AMBASSADOR trial and 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 of the National Cancer Institute. “This is long-awaited data in the bladder cancer community.”

AMBASSADOR (A031501) is a randomized, open-label Phase 3 trial evaluating pembrolizumab versus observation for the adjuvant treatment of localized MIUC and locally advanced urothelial carcinoma. The dual primary endpoints are OS and DFS, and secondary endpoints include OS and DFS in PD-L1 positive and negative patients. 

The trial enrolled 702 patients, randomized to receive pembrolizumab (200 mg intravenously every three weeks for up to 18 cycles) or undergo observation.

Effect of pembrolizumab therapy on primary endpoints

At a prespecified interim analysis review, pembrolizumab, an anti-PD-1 therapy, demonstrated a statistically significant and clinically meaningful improvement in disease-free survival (DFS) versus 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 DFS or death by 31 percent versus observation in patients after surgery. Median DFS was 29.0 months for pembrolizumab and 14.0 months for observation, an improvement of 15 months. 

These DFS results were consistent regardless of patients’ PD-L1 expression status. The trial’s other dual 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 data mature. After a median follow-up of 36.9 months, the median OS was 50.9 months for pembrolizumab versus 55.8 months for observation. 

Safety profile of pembrolizumab

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 (side effects that are severe or medically significant but not immediately life-threatening) occurred in 48.4 percent of patients receiving pembrolizumab versus 31.8 percent of patients under observation.

17.4 percent of patients receiving pembrolizumab withdrew from the trial without event, versus 27.2 percent from the observation arm. Some 76 patients (22 percent) in the observation arm subsequently received an immune checkpoint inhibitor.

- This press release was originally published on the Alliance for Clinical Trials in Oncology website