Perioperative Durvalumab Plus Enfortumab Vedotin Improves Survival in Cisplatin-Ineligible MIBC

A perioperative regimen of durvalumab (Imfinzi) combined with neoadjuvant enfortumab vedotin (EV; Padcev) elicited statistically significant and clinically meaningful improvements in both event-free survival (EFS) and overall survival (OS) vs standard of care in patients with muscle-invasive bladder cancer (MIBC) who were ineligible for or had declined cisplatin-based chemotherapy, according to findings from the phase 3 VOLGA trial.¹

These high-level data from a planned interim analysis of the VOLGA trial have not yet been made available and are expected to be presented at an upcoming medical meeting and submitted to regulatory authorities.

"Up to half of patients with muscle-invasive bladder cancer are not eligible for cisplatin and face high rates of disease recurrence, even after having their bladder removed, leaving a significant need for new effective and well-tolerated treatments. The VOLGA results show that perioperative durvalumab significantly extends event-free survival and overall survival when combined with neoadjuvant enfortumab vedotin, with a manageable safety profile, compared to surgery for patients in this curative-intent setting," Thomas Powles, MD, international coordinating investigator for VOLGA, and professor and chair of Barts Cancer Centre at Queen Mary University of London, stated in a news release.¹ 

VOLGA Trial Design and Outcomes

VOLGA (NCT04960709) is a phase 3, randomized, open-label, multicenter global study evaluating 2 experimental perioperative regimens against standard of care (radical cystectomy with or without approved adjuvant treatment ) in patients with cisplatin-ineligible MIBC. The trial tests EV in combination with PD-L1 inhibition, with or without CTLA-4 inhibition, hypothesizing that EV may improve outcomes by downstaging disease before cystectomy, and that adjuvant therapy may further improve time to disease relapse.¹

The trial included 2 experimental arms: perioperative durvalumab plus neoadjuvant EV, and perioperative durvalumab plus tremelimumab (Imjudo) in combination with neoadjuvant EV. The dual primary end points are EFS and OS.

The high-level results from a planned interim analysis announced today showed perioperative treatment with durvalumab in combination with neoadjuvant EV demonstrated statistically significant and clinically meaningful improvements in EFS and OS in patients with MIBC vs standard of care.

Perioperative durvalumab plus tremelimumab in combination with neoadjuvant EV demonstrated a statistically significant and clinically meaningful improvement in EFS and a favorable trend for OS; however, the OS data were not statistically significant at this planned interim analysis and will be formally reassessed at a subsequent analysis.

The safety and tolerability profile was consistent with expectations. The safety and tolerability of durvalumab with or without tremelimumab plus EV was consistent with the known safety profiles of the individual medicines, with no new safety signals identified.

Looking Ahead

Durvalumab is FDA approved for use in combination with gemcitabine and cisplatin for the treatment of cisplatin-eligible MIBC patients in the perioperative setting.² EV plus pembrolizumab (Keytruda) is approved by the FDA for perioperative treatment of cisplatin-ineligible patients and is currently under priority review by the FDA for perioperative MIBC regardless of cisplatin eligibility, with a Prescription Drug User Fee Act target action date of August 17, 2026.³

"This interim analysis from the VOLGA trial highlights the benefit of perioperative [durvalumab] with neoadjuvant enfortumab vedotin compared to surgery, a novel regimen that optimizes treatment options for patients. Together with NIAGARA and POTOMAC, VOLGA is our third positive readout in bladder cancer, setting a strong foundation for [durvalumab] as the immunotherapy backbone in this early-stage, curative-intent setting," Susan Galbraith, executive vice president, Oncology Hematology R&D at AstraZeneca, stated in the news release.¹

REFERENCES

1. AstraZeneca. Perioperative Imfinzi plus neoadjuvant EV showed statistically significant and clinically meaningful improvements in event-free survival and overall survival in muscle-invasive bladder cancer in the Phase III VOLGA trial. Press release. May 14, 2026. https://tinyurl.com/4uspa7nx

2. U.S. Food and Drug Administration. FDA approves durvalumab for muscle invasive bladder cancer. FDA. March 28, 2025. Accessed May 14, 2026. https://tinyurl.com/5ak5e24a

3. Astellas Pharma/Pfizer. U.S. FDA grants priority review to sBLA for PADCEV + Keytruda as perioperative treatment for muscle-invasive bladder cancer regardless of cisplatin eligibility. News release. Astellas Pharma/Pfizer; April 20, 2026. Accessed May 14, 2026. https://tinyurl.com/mr4cn2hc