EU Approves Astellas' PADCEV and KEYTRUDA Combo for Advanced Urothelial Cancer

Astellas Pharma Inc. has announced that the European Commission has approved PADCEV™ (enfortumab vedotin), an antibody-drug conjugate, 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-containing chemotherapy. This approval is noteworthy as it marks the first regimen in advanced urothelial cancer to show superiority over the traditional platinum-containing chemotherapy, which has been the standard of care for nearly four decades.

The approval was primarily based on results from the Phase 3 EV-302 clinical trial, also known as KEYNOTE-A39. This trial 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. In the trial, the combination therapy achieved a median OS of 31.5 months compared to 16.1 months in the chemotherapy group, which translates to a 53% reduction in the risk of death. For PFS, the combination therapy resulted in 12.5 months versus 6.3 months for chemotherapy, indicating a 55% reduction in the risk of cancer progression or death.

Dr. Thomas Powles from the Barts Cancer Institute Biomedical Research Centre in the UK highlighted the significance of this new first-line treatment for advanced urothelial cancer. He noted that the treatment combination's effectiveness was evident during the clinical trial, wherein it significantly extended both overall survival and progression-free survival compared to traditional chemotherapy.

Alex Filicevas, Executive Director of the World Bladder Cancer Patient Coalition, emphasized the urgent need for new treatment options, noting Europe's high incidence of bladder cancer and the often late stage at which it is diagnosed. The new approval provides hope for better disease outcomes for these patients.

Ahsan Arozullah, MD, MPH, Senior Vice President and Head of Oncology Development at Astellas, expressed delight over the European Commission's approval, which aligns with recent updates to European clinical guidelines. This approval reflects Astellas' commitment and collaboration with clinical trial investigators, study participants, and the broader bladder cancer community. The company aims to ensure that patients across the European Union can benefit from this combination therapy early in their treatment journey.

Bladder cancer is the fifth most commonly diagnosed cancer in Europe, with more than 165,000 new cases and over 50,000 deaths annually. The Phase 3 EV-302 clinical trial assessed the efficacy and safety of the enfortumab vedotin and pembrolizumab combination in patients with previously untreated unresectable locally advanced or metastatic urothelial cancer. Approximately 30% of patients who completed chemotherapy in the trial continued with maintenance therapy using avelumab, a PD-L1 inhibitor, reflecting current real-world clinical practices.

The European Marketing Authorization for this combination therapy is valid across all 27 EU member states, as well as Iceland, Liechtenstein, and Norway. It aligns with the latest clinical guidelines from the European Society for Medical Oncology and the European Association of Urology, which recommend this combination as the first-line treatment for locally advanced or metastatic urothelial cancer.

Previously, in December 2023, the U.S. Food and Drug Administration (FDA) approved the combination therapy for treating adult patients with locally advanced or metastatic urothelial cancer. Additionally, in April 2022, the European Commission had approved enfortumab vedotin as a monotherapy for patients who had previously received platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor.

Bladder cancer, originating in the urothelial cells lining the urinary tract, is diagnosed in approximately 614,000 people worldwide annually and causes 220,000 deaths. Continuous treatment and surveillance make bladder cancer one of the most expensive cancers over a patient's lifetime. The approval of enfortumab vedotin in combination with pembrolizumab offers a significant advancement in the treatment landscape for this challenging disease.