Perioperative durvalumab plus enfortumab vedotin improves EFS in cisplatin-ineligible MIBC

Perioperative treatment with durvalumab (Imfinzi) in combination with neoadjuvant enfortumab vedotin-ejfv (Padcev) demonstrated statistically significant improvements in event-free survival (EFS) and overall survival (OS) vs standard-of-care in patients with cisplatin-ineligible muscle-invasive bladder cancer (MIBC), according to a planned interim analysis of the phase 3 VOLGA trial announced by AstraZeneca.¹

Patients in the standard-of-care comparator arm underwent radical cystectomy with or without approved adjuvant treatment.

Additionally, a separate treatment arm evaluating perioperative durvalumab plus tremelimumab-actl (Imjudo) in combination with neoadjuvant enfortumab vedotin also met the EFS end point and demonstrated a favorable OS trend. However, the OS findings for the triplet regimen did not meet statistical significance at the interim analysis and will be re-evaluated in a future assessment.

According to the company, the safety profile for the combination was consistent with the known safety profile of the individual agents. No new safety signals were observed in the trial.

“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, MD, MBBS, MRCP, professor and chair of Barts Cancer Institute (QMUL) in London, UK, and International Coordinating Investigator for the trial, in the news release.¹ “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.”

The company stated that full findings will be presented at an upcoming medical meeting and shared with global regulatory authorities.

About VOLGA

VOLGA (NCT04960709) is an open-label, global phase 3 trial evaluating perioperative durvalumab with or without tremelimumab in combination with enfortumab vedotin in patients with MIBC who were either ineligible for or declined cisplatin-based chemotherapy.²

The study enrolled patients with cT2-4aN0-1M0 urothelial carcinoma who were candidates for radical cystectomy. Participants also needed to have an ECOG performance status of 0-2 at the time of enrollment and no prior receipt of systemic chemotherapy or immunotherapy for MIBC.

Patients were randomly assigned to receive durvalumab plus enfortumab vedotin, durvalumab/tremelimumab plus enfortumab vedotin, or standard-of-care surgery with or without adjuvant therapy. The primary end points include EFS and safety. Secondary end points include pathologic complete response, OS, disease-free survival, and quality-of-life measures.

Clinical context

The VOLGA findings add to a growing body of research evaluating perioperative immunotherapy strategies in MIBC. In March 2025, the FDA approved durvalumab in combination with neoadjuvant gemcitabine and cisplatin followed by adjuvant durvalumab for adults with MIBC based on the phase 3 NIAGARA trial (NCT03732677). In that study, the regimen demonstrated significant improvements in EFS and OS compared with chemotherapy alone.

Similarly, in the phase 3 KEYNOTE-905/EV-303 trial (NCT03924895), perioperative enfortumab vedotin plus pembrolizumab (Keytruda) significantly extended EFS and OS vs surgery alone in patients with MIBC who are ineligible for cisplatin-based chemotherapy..

“Sadly, we will [have] to rely on cross-trial comparisons with KEYNOTE-905/EV-303, as head-to-head trials rarely happen in this setting,” noted Daniel Antonio González Padilla, MD, in correspondence with Urology Times^®. “Nevertheless, this is good news—new options with proven benefit in hard end points such as overall survival, or patient-reported outcomes like quality of life—are always welcome in our therapeutic armamentarium.”

Beyond NIAGARA and VOLGA, AstraZeneca previously reported positive disease-free survival findings from the POTOMAC trial (NCT03528694) evaluating durvalumab plus BCG in high-risk non–muscle-invasive bladder cancer.

“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,” said Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, in the news release. “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.”​

REFERENCES

1. Perioperative IMFINZI® (durvalumab) 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-us.com/content/az-us/media/press-releases/2026/Perioperative-IMFINZI-durvalumab-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.html

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. April 14, 2026. Accessed May 14, 2026. https://clinicaltrials.gov/study/NCT04960709