A new study presented at the ESMO Congress 2025 in Berlin suggests that combining the immunotherapy pembrolizumab with the targeted antibody–drug conjugate enfortumab vedotin could significantly improve outcomes for people with muscle-invasive bladder cancer (MIBC) who cannot receive cisplatin-based chemotherapy.
In the phase 3 trial KEYNOTE-905/EV-303, patients treated with this combination lived longer and remained cancer-free longer than those who had surgery alone. Researchers reported that this approach improved both event-free survival (the time patients lived without cancer returning or worsening) and overall survival.
The study involved 344 patients with MIBC who were ineligible for cisplatin-based chemotherapy. Those who received the combination treatment before and after surgery had a much higher rate of complete tumor disappearance—57 percent compared with about 9 percent for patients who had surgery alone. This improvement even surpassed results typically seen with chemotherapy.
Although side effects were more frequent in patients receiving the drug combination—mainly skin reactions, nerve issues, and thyroid changes—the overall benefits were considered clinically meaningful. Experts caution that the regimen may not be suitable for everyone, especially those with severe neuropathy, uncontrolled diabetes, or active autoimmune disease.
If confirmed in ongoing studies, this combined treatment could become a new standard of care for patients who cannot receive cisplatin. Future studies, including the VOLGA and KEYNOTE-B15/EV-304 trials, are now exploring how similar drug combinations could further improve bladder cancer treatment both before and after surgery.
Reference
Vulsteke C, et al. Perioperative (periop) enfortumab vedotin (EV) plus pembrolizumab (pembro) in participants (pts) with muscle-invasive bladder cancer (MIBC) who are cisplatin-ineligible: The phase 3 KEYNOTE-905 study. ESMO Congress 2025 – LBA2
