Data from the phase 3 KEYNOTE-905/EV-303 trial demonstrated that enfortumab vedotin (Padcev) combined with pembrolizumab (Keytruda), administered before and after surgery, significantly improved event-free survival (EFS), overall survival (OS), and pathological complete response (pCR) rates compared with surgery alone in patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin-based chemotherapy.
At the 2025 Society of Urology Oncology Annual Meeting in Phoenix, Arizona, Dr. Laura Bukavina, assistant professor of Urologic Oncology at Cleveland Clinic Glickman Urologic Institute, discussed the significance of these findings and highlighted remaining questions regarding the treatment regimen. She noted that the trial was well-designed, including a patient cohort representative of real-world clinical practice.
Dr. Bukavina described the results as very promising, with a pathological complete response rate of 57% and manageable toxicity consistent with expectations. She also noted anticipation for the results of the ongoing KEYNOTE-B15/EV-304 trial, which is evaluating the same combination in cisplatin-eligible patients. These results are expected to be comparable or slightly improved relative to the cisplatin-ineligible population.
An important unresolved issue is identifying which patients can safely preserve their bladder following treatment with enfortumab vedotin and pembrolizumab. Dr. Bukavina pointed out that clinical complete response does not reliably predict pathological complete response, while current diagnostic tools such as MRI, CT, and circulating tumor DNA have limitations in detecting residual disease.
She concluded that although the treatment shows strong efficacy and the potential to save many bladders, further work is needed to determine which patients will truly benefit from bladder preservation after therapy.
Reference:
Perioperative enfortumab vedotin plus pembrolizumab in participants with muscle-invasive bladder cancer who are cisplatin-ineligible: The phase III KEYNOTE-905 study. Presented at the 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
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