AstraZeneca’s VOLGA Trial Shows Survival Benefit for Perioperative Imfinzi Regimen in Muscle-Invasive Bladder Cancer

AstraZeneca announced positive high-level results from the Phase 3 VOLGA trial evaluating perioperative treatment regimens for patients with muscle-invasive bladder cancer (MIBC) who are ineligible for or declined cisplatin-based chemotherapy. The company reported that perioperative durvalumab (brand name Imfinzi) combined with neoadjuvant enfortumab vedotin (EV) demonstrated statistically significant and clinically meaningful improvements in event-free survival (EFS) and overall survival (OS) compared with standard-of-care surgery alone.¹

The planned interim analysis also showed that a second investigational regimen combining perioperative Imfinzi plus tremelimumab (brand name Imjudo) with neoadjuvant EV significantly improved EFS and demonstrated a favorable OS trend, although the OS endpoint did not reach statistical significance at the interim analysis.¹

Addressing an Unmet Need in Cisplatin-Ineligible Patients

The VOLGA trial enrolled patients with MIBC undergoing radical cystectomy who were either ineligible for or declined cisplatin chemotherapy, a population with historically limited treatment options. According to published literature, up to half of patients with MIBC may be unable to receive cisplatin because of renal impairment or other comorbidities.² Despite surgery, recurrence rates remain high in this patient population.³

“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,” said Thomas Powles, professor and chair of Barts Cancer Centre at Queen Mary University of London and international coordinating investigator for the VOLGA trial, in a press release. “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.”¹

Trial Design and Safety Findings

The open-label, multicenter global study enrolled 695 patients across 182 centers in 25 countries. Participants were randomized into three treatment arms comparing perioperative immunotherapy combinations against radical cystectomy with or without approved adjuvant treatment. Dual primary endpoints included EFS for both experimental arms versus the comparator arm, while secondary endpoints included OS, pathologic complete response, disease-free survival, and pathologic downstaging.⁴

According to AstraZeneca, the safety and tolerability profile of the regimens was consistent with the known profiles of the individual therapies, and no new safety signals were identified.¹

Broader Implications for Bladder Cancer Treatment

Susan Galbraith, executive vice president of Oncology Hematology R&D at AstraZeneca, said the findings further strengthen the company’s bladder cancer immunotherapy strategy.

“This interim analysis from the VOLGA trial highlights the benefit of perioperative Imfinzi with neoadjuvant enfortumab vedotin compared to surgery, a novel regimen that optimizes treatment options for patients,” Galbraith said in the company announcement. “Together with NIAGARA and POTOMAC, VOLGA is our third positive readout in bladder cancer, setting a strong foundation for Imfinzi as the immunotherapy backbone in this early-stage, curative-intent setting.”¹

Bladder cancer remains the ninth most common cancer worldwide, with more than 614,000 new cases diagnosed annually.¹ AstraZeneca stated that the VOLGA data will be presented at a future medical meeting and submitted to global regulatory authorities for review.

References

1. 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. (2026 May 14). AstraZeneca. https://www.astrazeneca.com/media-centre/press-releases/2026/imfinzi-ev-improves-efs-os-in-bladder-cancer.html
2. Pichler, R. et al. (2024 Jul 2). Defining cisplatin eligibility in patients with muscle-invasive bladder cancer. Oncology. https://pmc.ncbi.nlm.nih.gov/articles/PMC11546640/?utm_source=chatgpt.com
3. Treatment of Bladder Cancer, Based on the Stage and Other Factors. The American Cancer Society. https://www.cancer.org/cancer/types/bladder-cancer/treating/by-stage.html?utm_source=chatgpt.com
4. 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). (2026). Clinicaltrials.gov. https://clinicaltrials.gov/study/NCT04960709