A recent clinical trial has demonstrated that adjuvant treatment with pembrolizumab (Keytruda) significantly extends cancer-free survival in patients with high-risk, muscle-invasive bladder cancer following surgical removal of the bladder. The study, published in the New England Journal of Medicine, indicates that pembrolizumab nearly doubles the time patients remain cancer-free compared to observation alone, offering a new treatment option for this aggressive disease.
Improved Cancer-Free Survival with Pembrolizumab
The AMBASSADOR trial, led by researchers at the National Institutes of Health (NIH), involved 702 patients with high-risk, muscle-invasive bladder cancer who had undergone bladder-removal surgery. Participants were randomized to receive either pembrolizumab every three weeks for a year or observation. After a median follow-up of almost four years, the pembrolizumab group showed a median cancer-free survival of 29.6 months, compared to 14.2 months in the observation group.
"This study shows that pembrolizumab can offer patients another treatment option to help keep their disease from coming back," said lead investigator Andrea B. Apolo, M.D., of NIH’s National Cancer Institute (NCI) Research Center for Cancer Research. "Extending the time that these patients are cancer-free makes a big difference in their quality of life."
Current Treatment Landscape and Unmet Needs
Muscle-invasive bladder cancer requires aggressive treatment, typically involving surgical removal of the bladder. Adjuvant or neoadjuvant cisplatin-based chemotherapy is often administered to improve outcomes. However, many patients are ineligible for or unable to tolerate cisplatin-based chemotherapy, leaving them with limited options beyond careful monitoring for relapse. The FDA approved nivolumab (Opdivo) in 2021 as an adjuvant therapy, but additional options are needed to further improve outcomes.
Pembrolizumab Efficacy Across PD-L1 Status
The researchers also assessed the impact of PD-L1 expression on pembrolizumab efficacy. Among patients with PD-L1-positive tumors, those treated with pembrolizumab had a median cancer-free survival of 36.9 months, compared to 21 months in the observation group. In patients with PD-L1-negative tumors, the pembrolizumab group had a median cancer-free survival of 17.3 months, compared to nine months in the observation group. The study concluded that PD-L1 status should not be used to select patients for pembrolizumab treatment, as both groups experienced benefit.
Safety and Tolerability
Pembrolizumab was generally well-tolerated, with common side effects including fatigue, itching, diarrhea, and underactive thyroid. These findings align with the known safety profile of pembrolizumab in other cancer types.
Ongoing Research and Future Directions
While preliminary overall survival data at three years showed similar rates between the pembrolizumab and observation groups (61% vs. 62%), the researchers noted that many patients in the observation group subsequently received nivolumab, potentially confounding the results. Ongoing research is focused on exploring combination therapies with immune checkpoint inhibitors and identifying biomarkers to personalize adjuvant treatment strategies for patients with high-risk, muscle-invasive bladder cancer.
