In a significant advancement for bladder cancer treatment, the U.S. Food and Drug Administration (FDA) has approved a new combination therapy for adult patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin-containing chemotherapy. The approval, announced jointly by Pfizer Inc. and Astellas Pharma Inc., authorizes the use of PADCEV® (enfortumab vedotin-ejfv) in combination with Merck’s KEYTRUDA® (pembrolizumab) as a perioperative treatment—administered both before and after surgery.
This regulatory milestone marks the first and only FDA-approved perioperative regimen for this specific patient population, offering a potential new standard of care for individuals who previously had limited treatment options beyond surgery.
Unprecedented Clinical Trial Results
The FDA’s decision is underpinned by the compelling results of the pivotal Phase 3 EV-303 clinical trial (also known as KEYNOTE-905). The study demonstrated that the combination therapy significantly outperformed the current standard of care, which is surgery alone (cystectomy).
Key findings from the trial include:
- Reduced Risk of Disease Recurrence: The combination treatment resulted in a 60% reduction in the risk of disease recurrence, progression, or death compared to surgery alone (Hazard Ratio [HR]=0.40; p<0.0001).
- Improved Overall Survival: The regimen demonstrated a 50% reduction in the risk of death compared to surgery alone (HR=0.50; p=0.0002).
- Event-Free Survival (EFS): The probability of patients remaining event-free at the time of analysis was 74.7% for the combination arm, compared to just 39.4% for the surgery-only arm.
Today’s approval, granted months earlier than anticipated, ushers in a new era of treatment for cisplatin-ineligible patients with MIBC who have long been underserved by existing treatments,” Legos stated. “PADCEV plus pembrolizumab is the first and only FDA-approved perioperative treatment regimen to demonstrate a meaningful survival advantage compared to surgery alone.
Jeff Legos
Addressing a Critical Unmet Need
Muscle-invasive bladder cancer is an aggressive disease with a high rate of recurrence. Approximately half of patients with MIBC experience cancer recurrence even after bladder removal surgery. Furthermore, a significant portion of these patients are ineligible for cisplatin-based chemotherapy, the standard pre-surgical treatment, due to other health conditions.
Mechanism and Safety Profile
The therapy combines two distinct mechanisms of action:
- PADCEV: An antibody-drug conjugate (ADC) that targets Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.
- KEYTRUDA: An anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells.
Safety results from the EV-303 trial were consistent with previous reports for this combination, with no new safety signals identified. The most common adverse reactions reported (occurring in ≥20% of patients) included increased glucose, decreased hemoglobin, rash, fatigue, peripheral neuropathy, and urinary tract infections, among others. Grade 3 or higher adverse events occurred in 71.3% of patients in the combination arm compared to 45.9% in the surgery arm.
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Graduated from the University of Kerala with B.Sc. Botany and Biotechnology. Attained Post-Graduation in Biotechnology from the Kerala University of Fisheries and Ocean Science (KUFOS) with the third rank. Conducted various seminars and attended major Science conferences. Done 6 months of internship in ICMR – National Institute of Nutrition, Hyderabad. 5 years of tutoring experience.
