AstraZeneca's Imfinzi Plus Enfortumab Vedotin Improves Survival in Cisplatin-Ineligible Muscle-Invasive Bladder Cancer

Perioperative durvalumab (Imfinzi, AstraZeneca) plus neoadjuvant enfortumab vedotin improved event-free survival (EFS) and overall survival (OS) compared with radical cystectomy with or without approved adjuvant treatment in patients with muscle-invasive bladder cancer (MIBC) who were ineligible for or had refused cisplatin-based chemotherapy, AstraZeneca announced. The phase 3 VOLGA results were presented at the European Society for Medical Oncology Congress 2026 and published simultaneously in The New England Journal of Medicine.

According to AstraZeneca, up to half of patients with MIBC are not eligible for cisplatin because of impaired renal function or comorbidities, and radical cystectomy alone has historically been their standard treatment. Durvalumab, an anti-PD-L1 monoclonal antibody, is approved in more than 50 countries with neoadjuvant chemotherapy for cisplatin-eligible MIBC.

The randomized, open-label, multicenter VOLGA trial assigned 695 patients at 229 sites  in 25 countries 1:1:1 to 2 durvalumab-based experimental arms or the comparator arm. The reported results compare 233 patients who received 3 cycles of durvalumab and enfortumab vedotin before surgery, followed by 9 cycles of adjuvant durvalumab, with 229 patients in the comparator arm. In a planned interim analysis, the combination reduced the risk of progression, recurrence, not undergoing surgery, or death, the primary EFS endpoint, by 49% (hazard ratio, 0.51; 95% CI, 0.38-0.67). Estimated 2-year EFS was 64% vs 45%.

For OS, a key secondary endpoint, the combination reduced the risk of death by 42% (hazard ratio, 0.58; 95% CI, 0.40-0.83); estimated 2-year OS was 78% vs 69%, and median OS was not reached in either arm. Grade 3 or 4 adverse events from any cause occurred in 64% of patients receiving the combination and 44% in the comparator arm. AstraZeneca reported no new safety signals and said patient-reported quality of life was maintained after surgery. Results for the other experimental arm, which added tremelimumab (Imjudo, AstraZeneca), were not reported in the release. In the NEJM paper, that arm had an estimated 24-month EFS of 60.1% (hazard ratio vs control, 0.61; 95% CI, 0.47-0.80), and its OS difference vs control was not significant (hazard ratio, 0.77; 95% CI, 0.54-1.07; P = 0.12).

In September 2026, the FDA granted Priority Review to perioperative durvalumab plus neoadjuvant enfortumab vedotin for patients with MIBC who are ineligible for or have refused cisplatin-based chemotherapy.

Source: AstraZeneca. Perioperative Imfinzi plus neoadjuvant enfortumab vedotin reduced risk of recurrence by 49% and risk of death by 42% in muscle-invasive bladder cancer. Press release. AstraZeneca; October 24, 2026. Accessed October 25, 2026.