- In the Phase 3 EV-304 trial, statistically significant improvements in overall survival and pathological complete response were also observed, with over half of patients having no detectable disease at surgery
- The results, combined with the recent unprecedented data from the EV-303 trial, highlight the potential for this regimen to become a new standard of care for muscle-invasive bladder cancer patients, regardless of cisplatin eligibility
- First and only platinum-free regimen to significantly improve event-free and overall survival when used before and after surgery
Christopher Hoimes, DO, Director of the Bladder Cancer Program and Center for Cancer Immunotherapy at Duke Cancer Institute, and an EV-304 Principal Investigator
“Approximately half of patients with muscle-invasive bladder cancer experience disease recurrence even after having their bladder removed. The EV-304 results, combined with the EV-303 study, provide compelling evidence that perioperative enfortumab vedotin plus pembrolizumab may offer survival benefits in the curative setting for patients with muscle-invasive bladder cancer, highlighting a potential departure from platinum-based chemotherapy as a cornerstone of care."Overall survival was a key secondary endpoint in EV-304 and showed a 35% reduced risk of death in patients treated with perioperative enfortumab vedotin plus pembrolizumab versus neoadjuvant chemotherapy (HR of 0.65; 95% CI, 0.48-0.89; 1-sided p=.0029).i The combination also demonstrated a pathological complete response (pCR) rate of 55.8% compared with 32.5% pCR rate at the time of surgery (estimated difference 23.4%; 95% CI, 16.7-29.8; 1-sided p<.0001), indicating that more than half of patients treated with the combination had no detectable disease at the time of surgery.i EFS, OS, and pCR benefits were generally consistent across all pre-defined subgroups, including age, gender, PD-L1 status, clinical stage and geographic region.i
The safety profile for perioperative enfortumab vedotin plus pembrolizumab observed in EV-304 was consistent with prior experience with the combination, and there were no new safety signals. Grade ≥3 adverse events (AEs) due to any cause occurred in 75.7% of patients treated with perioperative enfortumab vedotin plus pembrolizumab compared to 67.2% of patients treated with neoadjuvant chemotherapy.i
Jeff Legos, PhD, MBA, Chief Oncology Officer, Pfizer
“For people with muscle‑invasive bladder cancer, a perioperative approach that avoids the need for platinum‑based chemotherapy has demonstrated significant survival benefits. These compelling data, reinforced by the unprecedented EV‑303 results, suggest a transformative opportunity to establish PADCEV plus pembrolizumab as the next standard of care if approved, and provide a meaningful step forward for patients and their families.”
Moitreyee Chatterjee-Kishore, PhD, MBA, Head of Oncology Development, Astellas
“The EV-304 study data further substantiate the role of enfortumab vedotin plus pembrolizumab in bladder cancer and demonstrate its potential to offer patients with muscle-invasive bladder cancer more time with their loved ones. We are delighted with these new data and remain committed to investigating therapies for challenging and hard-to-treat cancers, with a goal of bringing renewed hope to patients.”
Bladder cancer is the ninth most common cancer worldwide, diagnosed in more than 614,000 patients each year globally, including an estimated 85,000 people in the U.S.ii,iii MIBC represents approximately 30% of all bladder cancer cases.iv Even after undergoing curative intent surgery, half of patients with MIBC experience disease recurrence.v
PADCEV plus pembrolizumab is not currently approved for use as perioperative treatment in cisplatin-eligible patients with MIBC. PADCEV plus pembrolizumab was approved in November 2025 by the U.S. FDA for use as perioperative treatment in cisplatin-ineligible patients with MIBC, based on results from the EV-303 Phase 3 clinical trial (also known as KEYNOTE-905), which were recently published in the New England Journal of Medicine.
- Neoadjuvant and adjuvant enfortumab vedotin plus pembrolizumab for participants with muscle-invasive bladder cancer who are eligible for cisplatin: randomized, open-label, phase 3 KEYNOTE-B15 study. Abstract #LBA630. 2026 American Society of Clinical Oncology Genitourinary (ASCO GU) Congress.
- World Bladder Cancer Patient Coalition. GLOBOCAN 2022: Bladder cancer 9th most common worldwide. Accessed January 29, 2026. Available at: https://worldbladdercancer.org/news_events/globocan-2022-bladder-cancer-is-the-9th-most-commonly-diagnosed-worldwide/
- American Cancer Society. Cancer Facts & Figures 2025. Accessed January 29, 2026. Available at: https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/2025-cancer-facts-figures.html
- Bladder Cancer Awareness Network. What is Muscle Invasive Bladder Cancer? Accessed January 29, 2026. Available at: https://bcan.org/what-is-muscle-invasive-bladder-cancer/#:~:text=When%20tumors%20grow%20into%20or,Virginia%20Health%20System%20explain%20MIBC.
- Squires P, Cook EE, Song Y, Wang C, Zhang A, Seshasayee SM, Rogiers A, Li H, Mamtani R. Treatment Patterns, Disease Recurrence, and Overall Survival in Patients with Muscle-Invasive Bladder Cancer after Radical Cystectomy: A Population-Level Claims-Based Analysis. Clinical Genitourinary Cancer. 2025 Nov;102466. https://doi.org/10.1016/j.clgc.2025.102466.