Advancements in Perioperative Bladder Cancer Therapy: A Promising New Regimen

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion recommending approval of KEYTRUDA (pembrolizumab), including its subcutaneous formulation KEYTRUDA SC, combined with Padcev (enfortumab vedotin-ejfv) as neoadjuvant treatment followed by adjuvant continuation after radical cystectomy for adults with cisplatin-ineligible resectable muscle-invasive bladder cancer (MIBC). This recommendation rests on statistically significant improvements in event-free survival (EFS), overall survival (OS), and pathologic complete response (pCR) rate observed in the Phase 3 KEYNOTE-905 trial versus surgery alone. If granted marketing authorization by the European Commission, the regimen would represent the first PD-1 inhibitor plus antibody-drug conjugate (ADC) approach available for this population across the European Union, Iceland, Liechtenstein, and Norway, with a decision anticipated in the third quarter of 2026.

Compelling Survival and Response Outcomes from KEYNOTE-905

The KEYNOTE-905 trial demonstrated that the perioperative KEYTRUDA plus Padcev regimen reduced the risk of EFS events by 60 percent (hazard ratio 0.40; 95 percent confidence interval 0.28-0.57; p<0.0001), with median EFS not reached compared with 15.7 months for surgery alone. Overall survival risk was lowered by 50 percent (hazard ratio 0.50; 95 percent confidence interval 0.33-0.74; p=0.0002), and the pCR rate reached 57.1 percent versus 8.6 percent. These results, presented at the European Society for Medical Oncology Congress 2025 and published in The New England Journal of Medicine, underscore clinically meaningful benefits for patients who cannot receive cisplatin-based chemotherapy and currently face surgery alone as the primary option.

Collaborative Phase 3 Study Framework and Disease Burden

The recommendation derives from the Phase 3 KEYNOTE-905 trial (also designated EV-303), conducted in partnership with Pfizer and Astellas, which enrolled cisplatin-ineligible or cisplatin-declining patients with resectable MIBC and compared perioperative KEYTRUDA plus Padcev against surgery alone. In 2022, Europe recorded approximately 224,700 bladder cancer diagnoses and more than 70,300 deaths, with roughly 25 percent of new cases classified as MIBC; up to half of these patients are ineligible for cisplatin, leaving them with limited therapeutic choices. The trial’s design directly addresses this gap by evaluating treatment both before and after radical cystectomy, supported by the existing U.S. Food and Drug Administration approval of the same regimen in November 2025.

Potential Shifts in European Market Access and Reimbursement Strategies

For health economics and outcomes research (HEOR) professionals, the CHMP opinion signals a possible expansion of treatment pathways that could influence market access decisions, pricing negotiations, and reimbursement frameworks across EU member states. The demonstrated gains in EFS and OS, alongside elevated pCR rates, provide evidence that may support value demonstrations in health technology assessments, particularly for populations with high recurrence risk and constrained options. As Merck advances its broader genitourinary cancer portfolio through more than 50 ongoing trials, stakeholders may need to evaluate the regimen’s positioning relative to existing standards, considering both clinical outcomes and the logistical requirements of perioperative administration when determining coverage policies.