2026 ASCO GU Highlights: Bladder Cancer KEYNOTE-B15

Rahul Parikh, MD, PhD, a professor at the University of Kansas, KU Medical Center, discussed his interest in advances in bladder cancer treatment, highlighting an important late-breaking abstract to be presented at the 2026 ASCO Genitourinary Cancers Symposium. The presentation, delivered by Matthew Galsky, MD, focuses on results from the phase 3 clinical trial KEYNOTE-B15, a study that could have significant implications for the management of muscle-invasive bladder cancer.

Dr Parikh explained that KEYNOTE-B15 (NCT04700124) is evaluating the role of perioperative enfortumab vedotin (Padcev), an antibody-drug conjugate, in combination with the immune checkpoint inhibitor pembrolizumab (Keytruda). This combination is being studied in patients with muscle-invasive bladder cancer who are eligible for cisplatin-based neoadjuvant chemotherapy. Currently, the standard of care for these patients typically involves cisplatin plus gemcitabine administered before surgery. In KEYNOTE-B15, this established regimen serves as the comparator arm, allowing investigators to determine whether the novel combination can improve outcomes over the existing standard.

He noted that enthusiasm for this approach stems from encouraging data seen in a related setting. In the KEYNOTE-905/EV-303 trial (NCT03924895), enfortumab vedotin plus pembrolizumab was studied in patients who were ineligible for cisplatin. In that earlier study, there was no widely accepted standard perioperative therapy, and many patients proceeded directly to radical cystectomy. The trial evaluated approximately 3 cycles of enfortumab vedotin plus pembrolizumab before surgery, followed by surgery and then 6 additional cycles of the combination postoperatively.

The combination demonstrated a significant improvement in event-free survival compared with surgery alone. In fact, the median event-free survival was not reached in the treatment arm, whereas it was 15.7 months in the radical cystectomy arm. The hazard ratio was approximately 0.4, indicating a substantial reduction in the risk of disease-related events. Based on these findings, the combination has received FDA approval for patients who are cisplatin-ineligible.

According to Dr Parikh, KEYNOTE-B15 represents the logical next step: determining whether this combination can outperform the established cisplatin-gemcitabine regimen in cisplatin-eligible patients. He emphasized that the oncology community will be particularly interested in pathologic complete response rates, overall response rates, and the safety profile of the regimen. The presentation may help clarify whether this combination could redefine the perioperative standard of care in muscle-invasive bladder cancer.