Astellas Pharma India today announced that the Central Drugs Standard Control Organization (CDSCO) has approved PADCEV (enfortumab vedotin) in combination with pembrolizumab for the first-line treatment of adult patients with unresectable or metastatic urothelial cancer who are eligible for platinum-containing chemotherapy. This marks the first approved regimen in India to demonstrate superiority over platinum-containing chemotherapy, which has been the standard of care for nearly 40 years.
Clinical Trial Evidence
The approval is based on the global Phase 3 EV-302 trial (also known as KEYNOTE-A39), which evaluated the combination in patients with previously untreated locally advanced or metastatic urothelial cancer. The study enrolled 886 patients regardless of PD-L1 status. Results showed that the combination nearly doubled median overall survival to 31.5 months compared to 16.1 months with chemotherapy, representing a 53% reduction in the risk of death (hazard ratio 0.47; 95% CI: 0.38-0.58; P<0.00001). Median progression-free survival was 12.5 months versus 6.3 months, a 55% reduction in risk of progression or death (hazard ratio 0.45; 95% CI: 0.38-0.54; P<0.00001).
Safety Profile
The safety results were consistent with previous reports from the EV-103 trial. Common Grade 3 or higher adverse events included maculo-papular rash, hyperglycemia, neutropenia, peripheral sensory neuropathy, diarrhea, and anemia. No new safety signals were identified.
Global Approvals and Significance
Enfortumab vedotin plus pembrolizumab has also been approved in the US, Europe, Canada, Australia, and several Asian countries. The EV-302 findings were presented at the 2023 ESMO Congress and published in the New England Journal of Medicine.
About PADCEV
PADCEV (enfortumab vedotin) is a first-in-class antibody-drug conjugate targeting Nectin-4, a protein highly expressed in bladder cancer. Its mechanism involves binding to Nectin-4-expressing cells, internalization, and release of monomethyl auristatin E, leading to cell cycle arrest and apoptosis. It is also approved as monotherapy for patients previously treated with platinum-containing chemotherapy and a PD-1/PD-L1 inhibitor.
This approval offers a new treatment option for patients with advanced urothelial cancer, addressing a significant unmet need.
