Merck announced that the U.S. Food and Drug Administration (FDA) has approved KEYTRUDA® (pembrolizumab) and KEYTRUDA QLEX™, in combination with Padcev® (enfortumab vedotin-ejfv), as neoadjuvant treatment followed by adjuvant therapy after cystectomy for adults with muscle-invasive bladder cancer (MIBC) who cannot receive cisplatin. This marks the first PD-1 inhibitor plus ADC regimen approved for this high-risk group.
Strong Evidence from Phase 3 KEYNOTE-905 Trial
As per the Merck Press release, these approvals stem from the Phase 3 KEYNOTE-905 (EV-303) trial, conducted with Pfizer and Astellas. After a median follow-up of 25.6 months, KEYTRUDA plus Padcev reduced the risk of event-free survival (EFS) events by 60% versus surgery alone and improved overall survival (OS) by 50%. The combination also achieved a markedly higher pathological complete response rate of 57.1%, compared with 8.6% in the control group.
Expert Insights on Clinical Impact
Dr. Matthew Galsky of Mount Sinai noted that many MIBC patients face recurrence after bladder removal and cannot receive cisplatin. Therefore, these results offer a “practice-changing advance.” Dr. Marjorie Green of Merck added that patients now have the flexibility to receive immunotherapy intravenously or subcutaneously.
Trial Design and Treatment Details
KEYNOTE-905 evaluated perioperative KEYTRUDA with or without Padcev versus surgery alone in 344 cisplatin-ineligible patients. Participants received three cycles of neoadjuvant therapy followed by cystectomy and optional adjuvant treatment. Tumor assessments included CT/MRI, cystoscopy and cytology post-surgery.
Safety Profile and Key Considerations
Common adverse reactions included rash, fatigue, pruritus, peripheral neuropathy, diarrhea, and appetite loss. Serious immune-mediated reactions may occur at any stage, requiring prompt identification and management. KEYTRUDA QLEX is contraindicated in patients with hypersensitivity to its components, and both products may cause fetal harm.
Overall, the approval provides a long-awaited therapeutic option for MIBC patients who previously had limited treatment choices.