Pfizer and Astellas combination therapy cuts bladder cancer recurrence risk by 60%

Pfizer and Astellas have reported positive results from the pivotal Phase 3 EV-303 clinical trial for PADCEV™ (enfortumab vedotin) in combination with KEYTRUDA™ (pembrolizumab). The study evaluated the combination in patients with muscle-invasive bladder cancer (MIBC) who are ineligible for or declined cisplatin-based chemotherapy. The treatment regimen, administered both before and after surgery, significantly improved event-free survival (EFS) and overall survival (OS) compared to surgery alone.

The primary endpoint of EFS showed a 60% reduction in the risk of tumor recurrence, progression, or death for patients receiving neoadjuvant and adjuvant PADCEV plus KEYTRUDA, compared to surgery alone. The median EFS had not yet been reached in the combination arm, whereas it was 15.7 months for the surgery-only arm. Two-year event-free rates were 74.7% for the combination versus 39.4% for surgery alone.

Key secondary endpoint results for OS demonstrated a 50% reduction in the risk of death for the PADCEV plus KEYTRUDA combination therapy. The median OS had not been reached for the combination arm, compared to 41.7 months for the surgery arm. The two-year survival rate was 79.7% for the combination group, versus 63.1% for the surgery-only group.

Safety findings from the EV-303 trial were consistent with previously reported data for this combination. The most common adverse events (≥30%) in the combination arm included pruritus, alopecia, diarrhea, fatigue, and anemia. Grade 3 or higher adverse events occurred in 71.3% of patients on the combination therapy and 45.9% of patients who received surgery alone.

These results suggest the PADCEV plus KEYTRUDA combination could redefine the standard of care for patients with cisplatin-ineligible muscle-invasive bladder cancer, offering a new treatment option where options have been limited.