The US FDA has expanded its nod of global pharma giant Pfizer and Astellas' PADCEV, in combination with Keytruda, making it the first platinum-free perioperative treatment for adults with muscle-invasive bladder cancer.
The expanded indication allows the combination to be used before and after surgery, broadening an earlier approval that was limited to cisplatin-ineligible patients.
The decision is based on results from the Phase 3 EV-304 (KEYNOTE-B15) trial, which showed the regimen -- PADCEV (enfortumab vedotin-ejfv) and Keytruda (pembrolizumab) --significantly outperformed standard cisplatin-based chemotherapy.
The study demonstrated a 47% reduction in the risk of tumor recurrence, progression or death, a 35% reduction in the risk of death, and a pathological complete response rate of 55.8% compared with 32.5% for chemotherapy. At two years, 79.4% of patients receiving PADCEV plus pembrolizumab remained event-free versus 66.2% of those receiving standard treatment.
"For muscle-invasive bladder cancer, a comprehensive treatment approach is important; the neoadjuvant phase can help shrink the tumor and target undetectable cancer cells early before surgery, while the adjuvant phase can be critical in eliminating residual, undetectable cancer cells following surgery.
"These data from EV-304 and this approval show that by delivering this regimen across both the neoadjuvant and adjuvant phases, without platinum-based chemotherapy, we can significantly reduce the risk of recurrence and improve overall survival — offering a potential new standard of care for adult patients with muscle-invasive bladder cancer," said Christopher Hoimes, EV-304 Principal Investigator.
The approval marks the first platinum-free regimen for this patient population in nearly 25 years and builds on the combination's growing role in bladder cancer treatment.
Aamir Malik, Executive Vice President, Chief US Commercial Officer, Pfizer, said: "...approval marks a historic turning point for the treatment of muscle-invasive bladder cancer, providing adult patients with the first approved platinum-free combination regimen shown to significantly improve survival over the current standard of care – regardless of cisplatin-eligibility.
"PADCEV plus pembrolizumab has established itself as the standard of care for first line therapy of advanced stages of bladder cancer, and we’re thrilled to be able to provide this community a much-needed new treatment option in an earlier, potentially curative-intent setting."
The EV-304 trial compared perioperative PADCEV plus pembrolizumab with standard neoadjuvant gemcitabine and cisplatin followed by surgery in cisplatin-eligible patients. Participants receiving the combination completed treatment before and after surgery, with nine planned cycles of PADCEV and 17 cycles of pembrolizumab.
