Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura) has announced that the European Commission has granted Marketing Authorization for PADCEV™ (enfortumab vedotin, an antibody-drug conjugate [ADC]) in combination with KEYTRUDA® (pembrolizumab, a PD-1 inhibitor) for the first-line treatment of adult patients with unresectable or metastatic urothelial cancer who are eligible for platinum-based chemotherapy.
This approval is based on the Phase 3 EV-302 clinical trial (also known as KEYNOTE-A39), which demonstrated that the combination of enfortumab vedotin and pembrolizumab nearly doubled the median overall survival (OS) and significantly extended progression-free survival (PFS) compared to platinum-based chemotherapy.
Dr. Thomas Powles from Barts Cancer Institute Biomedical Research Centre, UK, stated, “The introduction of a new, effective first-line treatment for advanced urothelial cancer marks a significant advancement in managing this typically fatal disease. The Phase 3 clinical trial showed impressive results, with enfortumab vedotin and pembrolizumab significantly extending overall and progression-free survival compared to traditional chemotherapy. I am eager to see this treatment implemented as a first-line option in clinical practice.”
Alex Filicevas, Executive Director of the World Bladder Cancer Patient Coalition, highlighted the urgency for new treatments, saying, “Despite Europe having the highest rates of new bladder cancer cases globally, awareness remains low, leading to many patients being diagnosed only at advanced stages. New treatment options are crucial for improving outcomes and offering hope to the bladder cancer community.”
Ahsan Arozullah, MD, MPH, Senior Vice President and Head of Oncology Development at Astellas, commented, “We are thrilled that the European Commission has approved enfortumab vedotin in combination with pembrolizumab as a first-line treatment for unresectable or metastatic urothelial cancer, aligning with recent updates to European clinical guidelines. This approval reflects our commitment to our partners, clinical trial participants, and the broader bladder cancer community. We look forward to patients across the EU benefiting from this combination early in their treatment.”
Bladder cancer is the fifth most common cancer in Europe, with over 165,000 new cases and more than 50,000 deaths annually. Often diagnosed late, many patients present with advanced or metastatic disease, where survival rates are particularly poor.
The Phase 3 EV-302 trial evaluated the efficacy and safety of enfortumab vedotin in combination with pembrolizumab for patients with previously untreated unresectable locally advanced or metastatic urothelial cancer (la/mUC). The results showed that the combination therapy achieved a median OS of 31.5 months compared to 16.1 months with platinum-based chemotherapy, representing a 53% reduction in the risk of death. The median PFS was 12.5 months with the combination compared to 6.3 months with chemotherapy, indicating a 55% reduction in the risk of cancer progression or death. Approximately 30% of patients in the trial completed chemotherapy and subsequently received maintenance therapy with avelumab, a PD-L1 inhibitor, reflecting current clinical practice. These findings were presented at the 2023 European Society for Medical Oncology (ESMO) Congress and published in the New England Journal of Medicine.
The European Marketing Authorization is applicable across all 27 EU member states, as well as Iceland, Liechtenstein, and Norway, and aligns with the updated clinical guidelines from the European Society for Medical Oncology and the European Association of Urology, which recommend enfortumab vedotin in combination with pembrolizumab as a first-line treatment for locally advanced or metastatic urothelial cancer. Astellas is collaborating with local regulatory authorities and health technology assessment bodies throughout the EU to ensure timely access to this treatment combination for eligible patients.
