Can enfortumab vedotin and pembrolizumab help muscle-invasive bladder cancer patients who cannot take cisplatin?
For patients with muscle-invasive bladder cancer (MIBC) who cannot take cisplatin, the standard treatment has been surgery alone. A recent phase 3 trial tested whether adding a combination of enfortumab vedotin (an antibody-drug conjugate) and pembrolizumab (an immunotherapy) before and after surgery could improve outcomes. The answer is yes: this combination significantly improved event-free survival and overall survival compared to surgery alone.
What the research says
A phase 3 trial published in 2026 randomly assigned 344 cisplatin-ineligible MIBC patients to receive either perioperative enfortumab vedotin plus pembrolizumab followed by surgery, or surgery alone 9. At a median follow-up of 25.6 months, the estimated 2-year event-free survival was 72.5% in the combination group versus 51.8% in the surgery-only group 9. The combination also improved overall survival and led to a higher rate of pathological complete response (no cancer cells found in the surgical specimen) 9. These findings are supported by earlier phase 2 studies that suggested pembrolizumab alone or in combination could be effective neoadjuvant therapy for MIBC 10. A 2025 review highlighted the combination of enfortumab vedotin and pembrolizumab as a top advance in bladder cancer, noting it doubled overall survival in metastatic disease 11. However, the sources do not directly compare this combination to other cisplatin-free options, and the trial's follow-up is still relatively short.
What to ask your doctor
- Is perioperative enfortumab vedotin plus pembrolizumab an option for my specific type of muscle-invasive bladder cancer?
- What are the potential side effects of this combination, and how do they compare to surgery alone?
- How does my kidney function and overall health affect my eligibility for this treatment?
- Are there any ongoing clinical trials for cisplatin-ineligible patients that I might consider?
- What is the expected recovery time and follow-up schedule if I choose this approach?
This question is drawn from common patient questions about this topic and answered using cited medical research. We do not provide individualized advice.