Pfizer and Astellas’ PADCEV® Plus KEYTRUDA® Effective Long-Term in Advanced Urothelial Cancer Treatment

Pfizer Inc. and Astellas Pharma Inc. have announced further results from the EV-302 Phase 3 clinical trial, which assesses the performance of their combined drug regimen, enfortumab vedotin plus pembrolizumab, against chemotherapy in treating patients with previously untreated locally advanced or metastatic urothelial cancer (la/mUC). These new results, gathered after almost 30 months of follow-up, continue to show that the drug combination significantly outperforms traditional chemotherapy.

The EV-302 trial, also referred to as KEYNOTE-A39, demonstrated that enfortumab vedotin and pembrolizumab together offer a marked improvement in overall survival (OS) and progression-free survival (PFS) compared to chemotherapy. Specifically, the median overall survival for the drug combination was 33.8 months, compared to 15.9 months for chemotherapy. This indicates the combination therapy reduced the risk of death by 49% compared to chemotherapy, with a hazard ratio of 0.51. The risk of disease progression or death was similarly reduced by 52% with the combination therapy, with a hazard ratio of 0.48. In all predefined subgroups of patients, including those eligible and ineligible for cisplatin, the combination therapy showed consistent benefits.

The safety profile of enfortumab vedotin and pembrolizumab remains consistent with previous analyses, with no new safety concerns identified. Among patients evaluable for response, the confirmed objective response rate for the combination was 67.5%, compared to 44.2% for chemotherapy. Median duration of response for the drug combination was reported at 23.3 months, significantly longer than the 7.0 months observed with chemotherapy. Additionally, a complete response was achieved in 30.4% of patients receiving the combination therapy, compared to 14.5% in those undergoing chemotherapy.

Leading figures in the oncology field, such as Professor Thomas Powles of Queen Mary University of London, have highlighted the significance of these findings, emphasizing that the results reinforce the potential of this combination as the standard first-line treatment for locally advanced or metastatic urothelial cancer. Dr. Roger Dansey of Pfizer noted that these results are a significant step forward for patients with advanced bladder cancer, who have traditionally faced poor prognoses and limited treatment options. Dr. Ahsan Arozullah from Astellas also emphasized that this combination offers a potent alternative to the platinum-based chemotherapies that have long been standard treatment for this cancer type.

The EV-302 trial is extensive, with 886 patients involved, and encompasses a wide demographic of patients, regardless of their PD-L1 status. This broadens the applicability of the trial results, confirming the treatment's effectiveness across diverse patient populations.

The collaboration between Pfizer, Astellas, and Merck has been pivotal in bringing this promising treatment alternative forward. Enfortumab vedotin combined with pembrolizumab has been approved in several countries, providing a new avenue of hope for patients afflicted with this challenging disease. This development is part of a larger clinical program investigating the potential of this drug combination in various stages of urothelial cancer and other solid tumors.

In summary, the extended follow-up data from the EV-302 trial accentuates the capacity of enfortumab vedotin plus pembrolizumab to significantly extend both survival rates and progression-free periods in patients with la/mUC, potentially reshaping the landscape of urothelial cancer treatment worldwide.