Postsurgical treatment with pembrolizumab (Keytruda) has shown to nearly double the length of time people with high-risk, muscle-invasive bladder cancer are cancer-free following surgical removal of the bladder, according to results from a large clinical trial. The study, led by researchers at the National Institutes of Health (NIH), was published Sept. 15, 2024, in the New England Journal of Medicine.
AMBASSADOR Trial Details
The AMBASSADOR trial randomly assigned 702 patients with high-risk, muscle-invasive bladder cancer who had undergone bladder-removal surgery to receive adjuvant therapy with pembrolizumab every three weeks for a year, or to observation for the same period of time. About two-thirds of the patients in the trial had completed neoadjuvant therapy with cisplatin.
After a median follow-up of almost four years, patients in the pembrolizumab group remained cancer-free for a median of 29.6 months, compared with 14.2 months for the observation group. Pembrolizumab was well tolerated, with the most common side effects being fatigue, itching, diarrhea, and an underactive thyroid.
Impact of PD-L1 Status
Researchers assessed whether the effect of pembrolizumab varied by PD-L1 status. Among the 404 patients whose tumors were PD-L1-positive, those treated with pembrolizumab remained cancer-free for a median of 36.9 months, compared with 21 months for those in the observation group. Among the 298 patients whose tumors were PD-L1-negative, those treated with pembrolizumab remained cancer-free for a median of 17.3 months, compared with nine months for the observation group. The researchers concluded that PD-L1 status should not be used to select patients for treatment with pembrolizumab, as both groups benefited from adjuvant pembrolizumab.
Overall Survival Data
In preliminary data on overall survival, at three years, about 61% of patients in the pembrolizumab group were still alive, compared with about 62% of patients in the observation group. The researchers pointed out that many patients in the observation group began taking nivolumab once it was approved or withdrew from the study, which may have skewed the results and made the overall survival data difficult to interpret.
Expert Commentary
“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 the Center for Cancer Research at NIH’s National Cancer Institute (NCI). “Extending the time that these patients are cancer-free makes a big difference in their quality of life.”
Future Directions
Research teams are already building on the study’s findings by exploring adjuvant treatment using various combinations of drugs with immune checkpoint inhibitors. Researchers are also testing biomarkers to identify patients with high-risk, muscle-invasive bladder cancer who could benefit most from adjuvant treatment of any kind and spare those who may not need it.
