Astellas Pharma and Seagen recently revealed that the US Food and Drug Administration (FDA) has granted priority review for the supplemental Biologics License Application (sBLA) concerning PADCEV (enfortumab vedotin-ejfv) in combination with KEYTRUDA (pembrolizumab) for treating adults with locally advanced or metastatic urothelial cancer (la/mUC).

In a groundbreaking EV-302 study, 886 previously untreated patients with locally advanced or metastatic urothelial carcinoma (la/mUC), regardless of PD-L1 expression, were randomly assigned to receive either PADCEV (1.25 mg/kg; IV) and KEYTRUDA (200 mg; IV) or gemcitabine with cisplatin or carboplatin. The primary goals were to assess progression-free survival (PFS) and overall survival (OS), alongside overall response rate (ORR) and safety. As of the August 8, 2023 data cutoff, the PADCEV-KEYTRUDA combination demonstrated a remarkable 55% risk reduction in progression or death (median PFS: 12.5 months vs. 6.3 months with chemotherapy). Moreover, the combo significantly extended OS, reducing the risk of death by 53%. The confirmed ORR for the PADCEV-KEYTRUDA combination stood at an impressive 67.7%, outperforming chemotherapy at 44.4%.

Grade ≥3 treatment-related adverse events (TRAEs) occurred in 56% with the combination and 70% with chemotherapy. The safety profile of the combo was generally manageable, with no new safety signals observed.

Conclusion

Platinum-based chemotherapy is the current standard for locally advanced or metastatic urothelial carcinoma (la/mUC), but long-term outcomes remain poor. The global Phase III study EV-302 introduced the PADCEV and KEYTRUDA combination as a potential game-changer for previously untreated la/mUC patients eligible for cisplatin or carboplatin. PADCEV-KEYTRUDA combo demonstrated significant improvements, nearly doubling median progression-free survival (PFS) and overall survival (OS) compared to chemotherapy, with a manageable safety profile and no new concerns. These findings position this combination as a compelling new standard of care for first-line la/mUC treatment.

For more insight into the patient's burden/epidemiology, treatment, and changing market landscape-related advancements of other related indications, refer to the following reports:

• Metastatic Urothelial Carcinoma Market Insight, Epidemiology And Market Forecast
• Urothelial Carcinoma Market Insight, Epidemiology And Market Forecast