AstraZeneca’s phase 3 VOLGA trial found lower hazards of an event and death with durvalumab plus enfortumab vedotin around surgery for patients unable or unwilling to take cisplatin.
Why cisplatin-free treatment matters
Muscle-invasive bladder cancer has grown into the bladder’s muscle wall and may have spread beyond what surgery can remove. For patients fit enough, treatment has often included cisplatin chemotherapy before bladder removal. But cisplatin may not be suitable for people with poor kidney function, hearing loss, nerve damage, heart problems or limited physical fitness. Durvalumab is approved around surgery with cisplatin-based chemotherapy, but that does not help patients who cannot take cisplatin.
VOLGA tested enfortumab vedotin, or EV, before surgery alongside durvalumab, followed by durvalumab after the operation. EV carries a cancer-killing drug to tumor cells; durvalumab is an immune checkpoint drug. The trial enrolled patients who could undergo bladder removal but were ineligible for or had declined cisplatin. Surgery remained central: this was not a bladder-preservation strategy. The control group had surgery, with or without approved postoperative treatment.
What the trial results show
At the planned interim analysis, the combination group had an event-free survival hazard ratio of 0.51 compared with the control group, meaning a 49% lower hazard of an event. An estimated 64% of patients in the combination group were alive without an event at two years, compared with 45% in the control group.
The hazard ratio for death was 0.58, a 42% lower hazard, and estimated two-year survival was 78% versus 69%. Median overall survival had not been reached in either group, so longer follow-up is needed. The 49% figure is not a drop in recurrence alone: event-free survival also counts progression, failure to reach surgery in some circumstances and death. The 42% figure is a relative hazard reduction; the two-year survival estimates differed by nine percentage points.
How it compares with another option
While VOLGA was underway, the FDA approved enfortumab vedotin plus pembrolizumab around surgery for cisplatin-ineligible patients in November 2025. In July 2026, approval expanded to adults with muscle-invasive disease who are candidates for bladder removal, regardless of cisplatin eligibility. The regimens share EV but use different checkpoint drugs, and VOLGA did not compare them directly. Results from separate trials are not a fair way to judge which works better.
VOLGA used three cycles of EV before surgery, with durvalumab continuing afterward. The approved pembrolizumab-EV approach also gives EV after surgery. That difference could appeal to some patients, but does not prove the VOLGA schedule is safer or easier to complete. EV risks include skin reactions, high blood sugar, nerve damage and lung inflammation; checkpoint drugs can cause serious immune reactions. AstraZeneca said VOLGA’s safety matched the drugs’ known profiles and reported no new safety signals.
What happens next
As of October 25, 2026, the FDA had granted Priority Review to AstraZeneca’s application for perioperative durvalumab plus EV for patients unable or unwilling to take cisplatin. The company anticipated an FDA decision in the fourth quarter. Priority Review speeds the process but is not approval.
If authorized, access will depend on the final label, clinician judgment, insurance coverage and whether patients can manage treatment while preparing for major surgery. VOLGA strengthens the case for another cisplatin-free option, but has not settled which perioperative regimen should come first.