(UroToday.com) The 2026 American Society of Clinical Oncology Genitourinary (ASCO) Annual Meeting, held in Chicago, IL, will host the Kidney and Bladder Cancer - Posters. Dr. Christopher J. Hoimes will present Abstract 4614: Neoadjuvant and adjuvant EV + P for participants with MIBC who are eligible for cisplatin: Randomized, open-label, phase 3 KEYNOTE-B15 study.
Enfortumab vedotin plus pembrolizumab has become the established first-line standard of care for patients with locally advanced/metastatic urothelial carcinoma and is now being explored in the perioperative setting for patients with MIBC. The phase 3 KEYNOTE-B15/EV-304 trial evaluated perioperative EV plus pembrolizumab compared with standard neoadjuvant gemcitabine plus cisplatin in cisplatin-eligible patients with MIBC.
This randomized phase 3 study enrolled patients with cT2-T4aN0M0 or T1-T4aN1M0 MIBC confirmed by central pathology and imaging review who were eligible for cisplatin-based chemotherapy and radical cystectomy with PLND. Patients were randomized 1:1 to receive either:
- Neoadjuvant EV 1.25 mg/kg on days 1 and 8 plus pembrolizumab 200 mg on day 1 every 3 weeks for 4 cycles, followed by RC + PLND and adjuvant EV plus pembrolizumab
- Neoadjuvant gemcitabine plus cisplatin for 4 cycles followed by RC + PLND
The primary endpoint was event-free survival (EFS) by blinded independent central review. Key secondary endpoints included pathological complete response (pCR) and overall survival (OS).
A total of 405 patients were randomized to EV plus pembrolizumab and 403 to gemcitabine/cisplatin. Median follow-up from randomization to the October 2025 data cutoff was 33.6 months.
Perioperative EV plus pembrolizumab significantly improved all major efficacy endpoints compared with gemcitabine/cisplatin:
- Median EFS was not reached versus 48.5 months
- Estimated 24-month EFS rates were 79.4% versus 66.2% (HR 0.53, 95% CI 0.41–0.70; P<0.0001)
- Estimated 24-month OS rates were 86.9% versus 81.3% (HR 0.65, 95% CI 0.48–0.89; P=0.0029)
- pCR rates were 55.8% versus 32.5% (difference 23.4%, 95% CI 16.7–29.8; P<0.0001)
Regarding safety, grade ≥3 treatment-emergent adverse events occurred in 75.7% of patients treated with EV plus pembrolizumab compared with 67.2% in the gemcitabine/cisplatin arm. The most common grade ≥3 adverse events of special interest included skin reactions related to EV (14.1%) and severe skin reactions associated with pembrolizumab (13.9%).
Key Messages:
- Perioperative enfortumab vedotin plus pembrolizumab significantly improved EFS, OS, and pCR rates compared with neoadjuvant gemcitabine plus cisplatin in cisplatin-eligible patients with MIBC
- The pCR rate exceeded 55% with EV plus pembrolizumab, representing a substantial improvement over standard chemotherapy
- Survival benefits were observed early and remained durable at a median follow-up of nearly 34 months
- The safety profile was consistent with prior experience with EV plus pembrolizumab, with no new safety signals identified
- These findings support perioperative EV plus pembrolizumab as an effective treatment option for cisplatin-eligible patients with MIBC
Presented by: Christopher Hoimes, DO, Duke University Medical Center, Durham, NC
Written by: Julian Chavarriaga, MD, Clinical Assistant Professor, Urologic Oncologist, Department of Urology at Penn State Health @chavarriagaj on X during the American Society of Clinical Oncology Genitourinary (ASCO) Annual Meeting held in Chicago, IL between May 29th and June 1st, 2026