EC approves PADCEV and KEYTRUDA combo for advanced urothelial cancer treatment

Astellas Pharma Inc. has announced a significant milestone in cancer treatment with the European Commission (EC’s) approval of PADCEV (enfortumab vedotin) combined with KEYTRUDA (pembrolizumab). This approval authorizes the use of this combination therapy as a first-line treatment for adult patients with unresectable or metastatic urothelial cancer who are eligible for platinum-based chemotherapy.

A New Era for Advanced Urothelial Cancer Treatment

The European Commission’s decision to approve this treatment combination is supported by compelling evidence from the Phase 3 EV-302 clinical trial, also known as KEYNOTE-A39. The trial results highlight the remarkable efficacy of enfortumab vedotin in conjunction with pembrolizumab. The data reveals that this combination nearly doubles the median overall survival (OS) compared to conventional platinum-based chemotherapy. Specifically, patients receiving the combined therapy experienced a median OS of 31.5 months, compared to 16.1 months for those on chemotherapy. Additionally, the combination treatment extended median progression-free survival (PFS) to 12.5 months versus 6.3 months with chemotherapy. This represents a 53% reduction in the risk of death and a 55% reduction in the risk of disease progression or death.

Dr. Thomas Powles of Barts Cancer Institute Biomedical Research Centre expressed optimism about the approval, noting its potential to transform the management of advanced urothelial cancer. “The approval of this treatment marks a new chapter for managing a disease that has long been challenging to treat effectively,” Dr. Powles said. He emphasized the significant survival benefits observed in the Phase 3 clinical trial, which highlight the treatment’s potential to improve patient outcomes.

Calls for Improved Awareness and Treatment Options

Alex Filicevas, Executive Director of the World Bladder Cancer Patient Coalition, emphasized the urgent need for effective treatments in Europe, where bladder cancer incidence rates are the highest globally. He pointed out the importance of raising awareness and improving early diagnosis, which could lead to better outcomes for patients. “New treatment options are crucial for improving survival rates and providing hope for patients battling advanced bladder cancer,” Filicevas remarked.

Astellas’ Senior Vice President and Head of Oncology Development, Ahsan Arozullah, welcomed the approval as a validation of their ongoing efforts and collaboration with the clinical community. “We are thrilled that this combination has been recognized as a first-line treatment option and look forward to its integration into clinical practice across the European Union,” Arozullah stated. He acknowledged the collective effort of researchers, trial participants, and advocacy groups in achieving this milestone.

Clinical Trial Details and Regulatory Context

The Phase 3 EV-302 trial was a randomized, open-label study designed to assess the efficacy and safety of enfortumab vedotin combined with pembrolizumab in patients with previously untreated, locally advanced or metastatic urothelial cancer. The trial enrolled 886 participants who were randomized to receive either the combination therapy or platinum-based chemotherapy. The primary endpoints of the trial were overall survival and progression-free survival, with secondary endpoints including objective response rate and duration of response.

The results of the trial, presented at the 2023 European Society for Medical Oncology (ESMO) Congress and published in the New England Journal of Medicine, demonstrated the combination therapy’s superior efficacy over chemotherapy. Approximately 30% of patients who initially received chemotherapy subsequently received maintenance therapy with avelumab, reflecting real-world clinical practices.

The European Commission’s approval aligns with updated guidelines from the European Society for Medical Oncology and the European Association of Urology, which now recommend enfortumab vedotin in combination with pembrolizumab as a first-line treatment for advanced urothelial cancer.

Global Perspective and Future Directions

This approval follows the U.S. Food and Drug Administration (FDA)’s December 2023 decision to approve the same combination for advanced urothelial cancer. Additionally, enfortumab vedotin was previously approved by the European Commission in April 2022 as a monotherapy for patients who had previously undergone platinum-based chemotherapy and PD-1 or PD-L1 inhibitors.

The EV-302 trial remains ongoing, continuing to evaluate the efficacy and safety of the treatment combination in a broader patient population. The trial’s dual primary endpoints and select secondary endpoints aim to further validate the benefits of this regimen.

The European Commission’s approval of PADCEV in combination with KEYTRUDA represents a significant advancement in the treatment of advanced urothelial cancer. This new regimen offers a promising alternative to traditional chemotherapy and aligns with recent clinical guidelines, paving the way for improved patient outcomes in Europe and beyond.