The European Commission approves KEYTRUDA plus Padcev for resectable muscle-invasive bladder cancer, following Phase 3 results showing improved survival and response.
Written By: Creola Gaonsalves, MS Biotech
Reviewed By: Pharmacally Editorial Team
Merck announced that the European Commission (EC) has approved KEYTRUDA® (pembrolizumab), its anti-PD-1 therapy, in combination with Padcev® (enfortumab vedotin-ejfv) as perioperative treatment for adults with resectable muscle-invasive bladder cancer (MIBC). Treatment is administered before surgery as neoadjuvant therapy and continued after radical cystectomy as adjuvant therapy. The approval also covers the subcutaneous formulation KEYTRUDA SC®, known as KEYTRUDA QLEX™ in the United States.
The authorization makes this the first PD-1 inhibitor plus antibody-drug conjugate (ADC) regimen approved in the European Union for patients with resectable MIBC regardless of cisplatin eligibility. The decision expands the available perioperative treatment options for a disease in which recurrence remains a significant concern.
Phase 3 KEYNOTE-B15 Results Support Approval
The EC decision is based on results from the Phase 3 KEYNOTE-B15 trial, also known as EV-304 (NCT04700124), conducted in collaboration with Pfizer and Astellas. The open-label, randomized trial enrolled 808 patients with previously untreated MIBC who were eligible for cisplatin-based chemotherapy.
Participants received perioperative KEYTRUDA plus Padcev and surgery, or neoadjuvant gemcitabine plus cisplatin followed by surgery. The primary endpoint was event-free survival (EFS), which captures events including disease progression, recurrence and death, according to the study definition.
After a median follow-up of 33.6 months, the combination reduced the risk of EFS events by 47% compared with chemotherapy and surgery (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.41–0.70; p<0.0001). Median EFS was not reached in the combination group, compared with 48.5 months in the chemotherapy group. At two years, the estimated EFS rates were 79.4% and 66.2%, respectively.
The trial also demonstrated a statistically significant overall survival (OS) benefit. KEYTRUDA plus Padcev reduced the risk of death by 35% compared with chemotherapy and surgery (HR, 0.65; 95% CI, 0.48–0.89; p=0.0029). The estimated two-year OS rates were 86.9% with the combination and 81.3% with chemotherapy.
Pathologic complete response (pCR), indicating no residual cancer detected in the surgical pathology assessment under the study definition, was also higher with the combination. The pCR rate was 55.8% with KEYTRUDA plus Padcev, compared with 32.5% with gemcitabine plus cisplatin (p<0.0001).
Together, these findings show improvements across measures of disease control, survival and response at surgery. However, the trial’s efficacy results were generated in cisplatin-eligible patients, an important distinction when interpreting the broader EU authorization.
Safety Findings and Clinical Context
Grade 3 or higher treatment-emergent adverse events occurred in 75.7% of patients receiving KEYTRUDA plus Padcev and 67.2% of those receiving chemotherapy and surgery. Treatment-related deaths were reported in two patients in the combination group and one patient in the comparator group. The efficacy findings therefore need to be considered alongside the regimen’s adverse-event profile and the clinical circumstances of individual patients.
The European Commission’s decision followed a positive recommendation from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) in September 2026. The authorization applies across the 27 EU member states, as well as Iceland, Liechtenstein and Norway. Commercial availability in individual countries will depend on national processes, including reimbursement procedures.
KEYTRUDA plus Padcev already has approvals for locally advanced or metastatic urothelial carcinoma in several markets. The new EU decision concerns its perioperative use in resectable MIBC and should be distinguished from those earlier indications.
Implications for Bladder Cancer Treatment
For eligible patients with resectable MIBC, perioperative treatment aims to address disease before surgery and reduce the risk of recurrence afterward. KEYNOTE-B15 provides evidence that combining PD-1 inhibition with an ADC can improve outcomes compared with neoadjuvant gemcitabine and cisplatin followed by surgery in cisplatin-eligible patients.
The broader EU authorization makes this treatment approach available regardless of cisplatin eligibility, although the pivotal efficacy comparison described above was conducted in cisplatin-eligible patients. The results support an important expansion of treatment options, while treatment decisions must still account for individual eligibility, potential toxicity, surgical planning and local clinical guidance.
Reference
European Commission Approves KEYTRUDA Plus Padcev as Perioperative Treatment for Adults with Resectable Muscle-Invasive Bladder Cancer (MIBC). Merck, October 21, 2026.
Perioperative Enfortumab Vedotin (EV) Plus Pembrolizumab (MK-3475) Versus Neoadjuvant Chemotherapy for Cisplatin-Eligible Muscle Invasive Bladder Cancer (MIBC) (MK-3475-B15/ KEYNOTE-B15 / EV-304) (KEYNOTE-B15), ClinicalTrials.gov ID NCT04700124
About the Writer
Creola Gonsalves (Linkedin) is an M.S. Biotechnology postgraduate with a strong interest in clinical research, evidence interpretation, and healthcare writing, with a focus on translating life-science knowledge into meaningful real-world insights.
She is trained in Good Clinical Practice (GCP), clinical research principles, and critical interpretation of randomized clinical trials, with certifications from NIH and Stanford University.
Her research background in biotechnological applications and microbial research strengthens her ability to understand scientific evidence and develop clear, accurate, and research-driven healthcare content.