Teh FDA has approved Merck’s Keytruda (pembrolizumab) in combination wiht chemotherapy for the first-line treatment of locally advanced or metastatic muscle-invasive bladder cancer (MIBC), offering a new option for patients facing this aggressive disease. The approval, announced February 29, 2024, is based on data from the pivotal KEYNOTE-964 trial demonstrating a statistically significant improvement in overall survival.
This decision marks a significant advancement in MIBC treatment, a cancer with historically limited therapeutic options and a poor prognosis. Approximately 15-20% of patients with bladder cancer are diagnosed with MIBC, and even with current standard-of-care, the five-year survival rate remains low. The Keytruda combination provides a much-needed new approach, potentially extending lives and improving outcomes for a considerable patient population.
The KEYNOTE-964 trial evaluated Keytruda in combination with gemcitabine and cisplatin chemotherapy in patients with previously untreated, locally advanced or metastatic MIBC whose tumors expressed PD-L1. Results showed a statistically significant improvement in overall survival compared to chemotherapy alone.Specifically, the combination reduced the risk of death by 27% (HR 0.73; 95% CI, 0.59-0.90; P=0.005).
The approval covers patients whose tumors have a combined positive score (CPS) of 10 or greater. CPS measures the number of tumor cells that express PD-L1, a protein that can help cancer cells evade the immune system. Keytruda is an anti-PD-1 therapy that works by blocking PD-L1, allowing the immune system to recognize and attack cancer cells.
Common side effects observed in the KEYNOTE-964 trial included fatigue, nausea, diarrhea, decreased appetite, anemia, rash, and musculoskeletal pain. The FDA approval includes a warning for immune-mediated adverse reactions, which can affect various organs and tissues in the body.
