Laura Bukavina, MD, highlights promise of EV/pembro and remaining questions on bladder preservation

Data from the phase 3 KEYNOTE-905/EV-303 trial (NCT03924895) demonstrated that enfortumab vedotin (Padcev) plus pembrolizumab (Keytruda) given before and after surgery yielded significant improvements in event-free survival (EFS), overall survival (OS), and pathological complete response (pCR) rate compared with surgery alone in patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin-based chemotherapy.¹

In an interview at the 2025 Society of Urology Oncology Annual Meeting in Phoenix, Arizona, Laura Bukavina, MD, MPH, offered her thoughts on the significance of these data and highlighted some remaining questions surrounding the regimen. Bukavina is assistant professor of Urologic Oncology at Cleveland Clinic Glickman Urologic Institute, and translational science lead in GU oncology at Cleveland Clinic Lerner College of Medicine in Cleveland, Ohio.

Bukavina began the discussion by explaining that the trial was well-designed in that it included a cohort of patients similar to what would be expected in a real-world setting.

On the findings, she noted, “The results were very promising, with a pathological CR rate of 57% and as expected toxicity.”

The field is now awaiting the results of the KEYNOTE-B15/EV-304 trial (NCT04700124), which is assessing the combination of enfortumab vedotin plus pembrolizumab in the cisplatin-eligible population. According to Bukavina, these results are expected to be comparable or slightly improved compared to what was seen in the cisplatin-ineligible population.

Buakavina also emphasized that another unresolved issue is determining which patients can safely preserve their bladder following treatment with EV/pembrolizumab. She explained that slinical complete response does not reliably equate to pathological complete response, and current tool such as MRI/CT and ctDNA have limitations in detecting residual disease.

Overall, she concluded, “We have a great drug. It works great. It's going to save many bladders, I'm sure. But the next question is, who are the patients who are actually getting their bladder saved?”

REFERENCE

1. Perioperative (periop) enfortumab vedotin (EV) plus pembrolizumab (pembro) in participants (pts) with muscle-invasive bladder cancer (MIBC) who are cisplatin-ineligible: The phase III KEYNOTE-905 study. Presented at: 2025 European Society for Medical Oncology Congress. October 17-21, 2025. Berlin, Germany. Abstract LBA2. https://s3.eu-central-1.amazonaws.com/m-anage.com.storage.esmo/static/esmo2025_abstracts/LBA2.html.pdf