Perioperative Durvalumab Plus Enfortumab Vedotin Improves Survival in MIBC

Perioperative treatment with durvalumab (Imfinzi) in combination with neoadjuvant enfortumab vedotin-ejfv (EV; Padcev) demonstrated statistically significant and clinically meaningful improvements in both event-free survival (EFS) and overall survival (OS) compared with standard of care in patients with muscle-invasive bladder cancer (MIBC) who were ineligible for or had declined cisplatin-based chemotherapy. This was announced in a press release from AstraZeneca on high-level results from a planned interim analysis of the phase 3 VOLGA trial (NCT04960709).¹

Patients who received perioperative durvalumab plus tremelimumab (Imjudo) and neoadjuvant EV also demonstrated a statistically significant improvement in EFS, with a favorable trend for OS. The investigators plan to reassess OS in this population at a later analysis.

How does perioperative durvalumab impact survival outcomes in MIBC?

In the planned interim analysis of the VOLGA trial, the combination of perioperative durvalumab and neoadjuvant EV (Arm 2) met its dual primary end points of EFS and OS. While specific hazard ratios for this trial will be presented at a forthcoming medical meeting, the findings may support this regimen as a potential new standard for patients who are ineligible for cisplatin. Additionally, a second experimental arm evaluating the triplet of perioperative durvalumab and tremelimumab plus neoadjuvant EV demonstrated a statistically significant and clinically meaningful improvement in EFS. However, while a favorable trend for OS was observed in Arm 1, the data did not reach statistical significance at the interim analysis and will be reassessed at a later date.

Thomas Powles, MD, professor and chair of Barts Cancer Centre and international coordinating investigator for the trial, emphasized the clinical necessity of these findings. He stated, “Up to half of patients with [MIBC] are not eligible for cisplatin and [experience] 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 [EFS] and [OS] when combined with neoadjuvant enfortumab vedotin, with a manageable safety profile, compared to surgery for patients in this curative-intent setting.”¹

What were the VOLGA trial eligibility and dosing requirements?

The randomized, open-label VOLGA trial enrolled 695 patients with MIBC who were planning to undergo radical cystectomy. To be eligible, patients must have been ineligible for cisplatin or have chosen to decline cisplatin-based chemotherapy. Patients were randomly assigned to 1 of 2 experimental perioperative arms or to the comparator arm, consisting of radical cystectomy with or without approved adjuvant treatment.

In the experimental duplet arm, patients received three 21-day cycles of neoadjuvant durvalumab plus EV, followed by surgery and nine 28-day cycles of adjuvant durvalumab monotherapy.² The triplet arm followed a similar neoadjuvant schedule with the addition of 2 cycles of tremelimumab, followed by surgery and 1 adjuvant cycle of tremelimumab alongside 9 cycles of durvalumab prior to surgery.

The primary end points were EFS and OS in the intent-to-treat population. Secondary end points included OS in the doublet arm vs the triplet arm and the doublet vs the comparator arm, pathologic complete response, disease-free survival, and pathologic downstaging across both experimental arms.

What are the safety and clinical implications of the VOLGA results?

The safety and tolerability of the durvalumab and EV-based regimens were consistent with the known profiles of the individual agents, with no new safety signals identified during the interim analysis.

Susan Galbraith, executive vice president of Oncology Research & Development at AstraZeneca, noted that VOLGA represents the third positive readout for durvalumab in bladder cancer, alongside NIAGARA (NCT03732677) and POTOMAC (NCT03528694). She remarked, “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.”¹

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. News release. AstraZeneca. May 14, 2026. Accessed May 15, 2026. https://tinyurl.com/2udpwysu
2. 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 15, 2026. https://tinyurl.com/54pnepfy