Breakthrough In Advanced Bladder Cancer Treatment: New Drug Combo Eliminates Need For Platinum-Based Chemotherapy

Muscle-invasive bladder cancer (MIBC) has long been treated with platinum-based chemotherapy, but a major clinical milestone is changing that landscape. Astellas Pharma and Pfizer recently announced game-changing results from their Phase 3 trial, demonstrating that a novel drug combination can outperform traditional chemotherapy while avoiding platinum-related toxicities.

A New Approach To Bladder Cancer Treatment

The trial evaluated PADCEV (enfortumab vedotin), a targeted antibody-drug conjugate that binds to Nectin-4, paired with Keytruda (pembrolizumab), an immunotherapy that activates the body’s immune system. What makes this combination particularly significant is its application around surgery—both as a preventive treatment before surgery and as a maintenance therapy afterward—rather than replacing surgery entirely.

Clinical Trial Results Show Dual Success

The 304 trial, formally known as KEYNOTE-B15, successfully achieved its primary goal: improving event-free survival (EFS)—the time before cancer recurrence or death occurs. Beyond this, the combination also demonstrated a statistically significant improvement in overall survival (OS), marking a rare accomplishment in cancer drug development where multiple survival endpoints are met simultaneously.

Additionally, patients receiving the PADCEV-Keytruda regimen showed higher pathologic complete response (pCR) rates compared to standard chemotherapy recipients. This metric measures how thoroughly the tumor is eliminated before surgery, suggesting deeper tumor control.

Why This Matters: A Platinum-Free Option

The most revolutionary aspect is that PADCEV plus Keytruda is the first platinum-free treatment regimen to improve both event-free and overall survival in patients with MIBC who are eligible for platinum-based therapy. This breakthrough eliminates the need for patients to endure platinum chemotherapy’s severe side effects—hearing loss, kidney damage, and peripheral neuropathy—while still achieving superior clinical outcomes.

The safety profile of the combination remained consistent with known characteristics, suggesting a manageable tolerability profile for patients.

Looking Forward

Combined with earlier positive findings from the EV-303 trial, these results suggest PADCEV plus Keytruda could establish a new standard of care for earlier-stage bladder cancer. Regulatory discussions with global health authorities are underway to support formal approval processes.