Rahway, N.J. — The European Commission has approved Merck’s Keytruda in combination with Padcev as a treatment before and after surgery for adults with resectable muscle-invasive bladder cancer who are ineligible for cisplatin-based chemotherapy.
The approval covers Keytruda, or pembrolizumab, and Keytruda SC in combination with Padcev, or enfortumab vedotin. Merck said it is the first and only PD-1 inhibitor and antibody-drug conjugate combination approved for these patients in the European Union.
The regimen is administered before radical cystectomy as neoadjuvant treatment and continued after surgery as adjuvant treatment.
The approval was based on results from the Phase 3 KEYNOTE-905 trial, also known as EV-303, conducted in collaboration with Pfizer and Astellas.
In the study, perioperative Keytruda plus Padcev reduced the risk of disease progression, recurrence, complications preventing surgery or death by 60% compared with surgery alone. Median event-free survival was not reached in the combination group, compared with 15.7 months for patients receiving surgery alone.
The combination also reduced the risk of death by 50%. Median overall survival was not reached in the Keytruda-Padcev group, compared with 41.7 months in the surgery-alone group.
The pathologic complete response rate was 57.1% among patients receiving the combination, compared with 8.6% among those undergoing surgery alone.
“Patients with resectable muscle-invasive bladder cancer who are ineligible for cisplatin-containing chemotherapy face an aggressive disease and few effective therapies, with surgery alone as the longstanding standard of care,” said Professor Christof Vulsteke, head of Integrated Cancer Center Ghent (IKG) and Clinical Trial Unit Oncology Ghent and KEYNOTE-905 principal investigator. “Based on robust data from the KEYNOTE-905 trial, this approval marks a turning point in bladder cancer care. It introduces a potentially practice-changing perioperative treatment option that may significantly improve outcomes and extend survival for this underserved patient population across the European Union.”
The European Medicines Agency’s Committee for Medicinal Products for Human Use recommended approval of the regimen in May.
“For patients with resectable muscle-invasive bladder cancer in Europe, this approval represents a meaningful advance after years of limited progress in the field,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. “As the first PD-1 inhibitor plus antibody-drug conjugate regimen approved in this setting, this treatment is poised to address a crucial unmet need, reflecting our continued commitment to delivering innovative KEYTRUDA-based therapies to patients with bladder cancer worldwide.”
The authorization applies across the European Union’s 27 member states, as well as Iceland, Liechtenstein and Norway. Commercial availability will vary by country and depend partly on national reimbursement procedures.
The U.S. Food and Drug Administration approved Keytruda and Keytruda QLEX, each in combination with Padcev, for the same treatment setting in November 2025.
KEYNOTE-905 enrolled 595 patients with muscle-invasive bladder cancer who were ineligible for or declined cisplatin-based chemotherapy. Participants were assigned to receive Keytruda before and after surgery, surgery alone, or Keytruda plus Padcev before and after surgery followed by Keytruda alone.
The trial remains underway to evaluate Keytruda alone compared with surgery alone.
