Perioperative durvalumab (Imfinzi) in combination with neoadjuvant enfortumab vedotin-ejfv (Padcev) produced statistically significant and clinically meaningful improvements in event-free survival (EFS) and overall survival (OS) vs standard-of-care (SOC) therapy in patients with cisplatin-ineligible or cisplatin-declining muscle-invasive bladder cancer (MIBC), according to findings from the phase 3 VOLGA trial (NCT04960709).1
Additionally, perioperative durvalumab plus tremelimumab (Imjudo) and neoadjuvant enfortumab vedotin displayed a statistically significant improvement in EFS vs SOC and a favorable trend for OS, however OS data were not statistically significant at the time of the planned interim analysis. These OS data will be formally reassessed at a subsequent analysis, according to a news release from AstraZeneca.
“Up to half of patients with MIBC 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,” Thomas Powles, MD, MBBS, MRCP, professor of genitourinary oncology, lead for solid tumor research, and director of Barts Cancer Centre at St. Bartholomew's Hospital in London, England, said in the release. “The VOLGA results show that perioperative durvalumab significantly extends EFS and OS when combined with neoadjuvant enfortumab vedotin, with a manageable safety profile, compared to surgery for patients in this curative-intent setting.”
Topline Data From VOLGA: Key Takeaways
- A planned interim analysis of the phase 3 VOLGA trial was positive for perioperative durvalumab plus neoadjuvant enfortumab vedotin in cisplatin-ineligible or cisplatin-declining MIBC.
- Statistically significant improvements in EFS and OS vs standard of care were reported.
- The safety profile of durvalumab with or without tremelimumab plus enfortumab vedotin was consistent with the known safety profiles of the individual agents. No new safety signals were identified.
How was VOLGA designed?
VOLGA was a randomized, open-label, multicenter global trial enrolling patients with MIBC who were undergoing radical cystectomy and were either ineligible for cisplatin or had declined cisplatin-based chemotherapy. To be eligible, patients also needed to be medically fit for cystectomy, have an ECOG performance status of 2 or less, and a life expectancy of at least 12 weeks at random assignment.2 The study was conducted across 182 centers in 25 countries in Europe, North America, South America, and Asia.1
Patients (n = 695) were randomly assigned 1:1:1 to 1 of 3 groups. Arm 1 comprised 3 cycles of durvalumab plus enfortumab vedotin before surgery, with 2 cycles of tremelimumab added in the neoadjuvant phase, followed by 9 cycles of adjuvant durvalumab plus 1 cycle of tremelimumab after cystectomy. Arm 2 consisted of 3 cycles of neoadjuvant durvalumab plus enfortumab vedotin followed by 9 cycles of adjuvant durvalumab monotherapy. Arm 3 was the comparator arm of radical cystectomy with or without approved adjuvant therapy.1,2
The trial had dual primary end points of EFS for each experimental arm vs the comparator arm.1 Secondary end points included OS, pathologic complete response, disease-free survival, and pathologic downstaging across both experimental arms.
What were the topline safety data in VOLGA?
The safety profile of durvalumab with or without tremelimumab plus enfortumab vedotin was consistent with the known safety profiles of the individual agents. No new safety signals were identified.
Data from VOLGA will be presented at a forthcoming medical meeting and shared with global regulatory authorities, according to the news release.
“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 [the phase 3] NIAGARA [NCT03732677] and POTOMAC [(NCT03528694) trials], 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.”
References
- 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.News release. AstraZeneca. May 14, 2026. Accessed May 14, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/imfinzi-ev-improves-efs-os-in-bladder-cancer.html
- Treatment combination of durvalumab, tremelimumab and enfortumab vedotin or durvalumab and enfortumab vedotin in patients with muscle invasive bladder cancer ineligible to cisplatin or who refuse cisplatin (VOLGA). ClinicalTrials.gov. Updated April 14, 2026. Accessed May 14, 2026. https://clinicaltrials.gov/study/NCT04960709
