VOLGA: AstraZeneca's Imfinzi Plus Enfortumab Vedotin Cuts Risk of Death by 42% in Bladder Cancer
Adding AstraZeneca's immunotherapy Imfinzi to enfortumab vedotin before bladder removal, then continuing Imfinzi after surgery, cut the risk of death by 42% in patients with muscle-invasive bladder cancer who cannot receive or have declined cisplatin chemotherapy. The Phase III VOLGA results were presented Saturday, Oct. 24, 2026, at the European Society for Medical Oncology (ESMO) Congress in Madrid and published at the same time in The New England Journal of Medicine. The readout arrives while the U.S. Food and Drug Administration is already reviewing the regimen under Priority Review.
Key developments
- Perioperative Imfinzi (durvalumab) plus neoadjuvant enfortumab vedotin (EV) reduced the risk of recurrence, progression, not undergoing surgery or death by 49% versus radical cystectomy with or without approved adjuvant treatment (event-free survival hazard ratio 0.51; 95% CI 0.38-0.67; p<0.0001).
- Overall survival improved with a hazard ratio of 0.58 (95% CI 0.40-0.83; p=0.0027). An estimated 78% of patients in the Imfinzi arm were alive at two years, compared with 69% in the comparator arm.
- Median event-free survival was not reached with the combination, versus 12.1 months in the comparator arm. Estimated two-year event-free survival was 64% versus 45%.
- Grade 3 or 4 adverse events from any cause occurred in 64% of patients on the combination and 44% in the comparator arm. AstraZeneca said no new safety signals emerged and patient-reported quality of life held up after surgery.
- The FDA granted Priority Review to the regimen in September 2026 for patients who are ineligible for or refuse cisplatin-based chemotherapy. AstraZeneca has not disclosed a target action date.
Disease and trial background
Muscle-invasive bladder cancer accounts for roughly one in four bladder cancer cases, according to AstraZeneca, which estimates that about 106,500 patients will be treated for the disease in 2026. The standard curative approach is cisplatin-based chemotherapy followed by removal of the bladder, but up to half of patients are not fit enough for cisplatin. For those patients, surgery alone has historically been followed by high recurrence rates. Thomas Powles, chair of Barts Cancer Centre in London and the trial's international coordinating investigator, presented the data in the meeting's Presidential Symposium I as late-breaking abstract LBA2.
VOLGA randomized 695 patients 1:1:1 at 182 sites in 25 countries. One arm received three cycles of Imfinzi plus EV before surgery and nine cycles of Imfinzi afterward (233 patients). A second arm added two pre-surgery doses of the CTLA-4 antibody Imjudo (tremelimumab). The comparator arm (229 patients) went straight to cystectomy, with or without approved adjuvant therapy. The data cutoff was March 2, 2026. AstraZeneca first disclosed in May that the trial had met its event-free and overall survival goals, without releasing the numbers.
The triple-drug arm told a different story. As reported by OncLive, it improved event-free survival (hazard ratio 0.61), but its overall survival hazard ratio of 0.77 did not reach statistical significance at this interim look. OncLive also reported a pathologic complete response rate of 45% with Imfinzi plus EV versus 10% in the control arm on local review.
Industry implications
VOLGA gives AstraZeneca a second route into the bladder cancer surgery setting. Its NIAGARA regimen, which pairs perioperative Imfinzi with cisplatin chemotherapy, is approved in more than 50 countries for cisplatin-eligible patients. VOLGA targets the patients NIAGARA leaves out. Susan Galbraith, AstraZeneca's head of oncology hematology R&D, framed the result as support for "the potential for IMFINZI to become the immunotherapy backbone treatment" across the disease.
The data also confirm a broader shift in bladder cancer care. Antibody-drug conjugates combined with checkpoint inhibitors are moving out of metastatic disease and into the curative setting, where treatment courses are fixed and patients are healthier. That shift raises the clinical stakes for drugmakers, since regimens given before and after surgery can redefine the standard of care for patients who might otherwise be cured by surgery alone.
Competitive and supply chain implications
AstraZeneca is not first in this space. The FDA approved Merck's Keytruda plus EV (sold as Padcev by Astellas and Pfizer) on Nov. 21, 2025, as perioperative treatment for cisplatin-ineligible muscle-invasive bladder cancer. That approval rested on the KEYNOTE-905/EV-303 trial in 344 patients, which reported an event-free survival hazard ratio of 0.40 and an overall survival hazard ratio of 0.50 versus surgery alone. Astellas and Pfizer have also reported positive results with the combination in cisplatin-eligible patients in the EV-304 trial, presented in February 2026.
The trials differ in design, populations and comparator treatment, so direct cross-trial comparisons are unreliable. The commercial dynamic is clearer. Both regimens depend on the same antibody-drug conjugate, which makes Astellas and Pfizer suppliers to both sides of the PD-1 versus PD-L1 contest. Physicians will likely weigh dosing schedules, safety and familiarity with each checkpoint inhibitor, while the higher rate of severe adverse events in the combination arm will draw attention to patient selection and supportive care.
Regional implications
The United States is the nearest market. Priority Review means FDA action could arrive well ahead of a standard review cycle, and U.S. urologists already use an EV-based perioperative regimen. VOLGA's global enrollment across 25 countries should support filings in other regions; AstraZeneca has said the data will be shared with regulators worldwide but has not named specific submissions outside the U.S.
In Europe, the Madrid presentation and the NEJM publication put the data in front of guideline committees. In the U.K., home to the trial's coordinating investigator, cisplatin is often unsuitable for older patients or those with impaired kidney function, making a non-cisplatin option relevant for health technology assessment bodies once a European filing advances.
Credence Research analysis
VOLGA strengthens AstraZeneca's position in bladder cancer, but it enters a market where Keytruda plus EV already set the reference point. The overall survival benefit on the two-drug arm is the strongest element of the readout, because survival data in the curative setting tend to carry the most weight with regulators and guideline panels. The failure of the Imjudo-containing arm to show a significant survival gain at this analysis is also informative: it suggests that adding a CTLA-4 antibody adds toxicity without a clear survival payoff here, which may simplify AstraZeneca's commercial focus to the two-drug regimen.
The safety numbers will matter as much as the efficacy figures. A 20-point gap in severe adverse events between arms is notable in a population that often includes older and frailer patients. Adoption is likely to depend on how centers manage EV-related toxicities before surgery and whether delays to cystectomy remain rare. For EV, the result widens its use regardless of which checkpoint inhibitor partner prevails, a durable position for Astellas and Pfizer.
What comes next
- FDA decision on perioperative Imfinzi plus neoadjuvant EV for cisplatin-ineligible or cisplatin-refusing patients, under Priority Review granted in September 2026.
- Submissions to other regulators, which AstraZeneca has said will receive the VOLGA data.
- A later overall survival analysis for the Imfinzi, Imjudo and EV arm, which did not reach significance at the interim cut.
- Guideline updates following the NEJM publication and the ESMO presentation.
- Potential filings for EV plus Keytruda in cisplatin-eligible patients based on EV-304, which Astellas and Pfizer said they would discuss with health authorities.
Sources
- AstraZeneca US newsroom: VOLGA Phase III results at ESMO 2026 (Oct. 24, 2026)
- U.S. FDA: Approval of pembrolizumab with enfortumab vedotin for muscle-invasive bladder cancer (Nov. 21, 2025)
- OncLive: Durvalumab plus enfortumab vedotin improves survival in cisplatin-ineligible MIBC (Oct. 24, 2026)
- Pfizer and Astellas: EV-304 results in cisplatin-eligible MIBC (Feb. 27, 2026)
Image: AstraZeneca building in Cambridge, England, by FDV via Wikimedia Commons, CC BY-SA 4.0. Cropped and edited by Credence Research.
About the Author
Senior News Editor at Credence Research Inc