The US Food and Drug Administration (FDA) approved durvalumab (Imfinzi, AstraZeneca) in combination with enfortumab vedotin-ejfv as neoadjuvant treatment, followed by single-agent durvalumab as adjuvant treatment following radical cystectomy among adults with muscle-invasive bladder cancer (MIBC) who are ineligible for or have refused cisplatin-based chemotherapy.
Announced on November 13, 2026, the approval followed findings from the randomized, open-label VOLGA trial, in which 695 patients with MIBC who were candidates for radical cystectomy but were ineligible for or refused cisplatin-based chemotherapy were randomly assigned 1:1:1 to receive neoadjuvant durvalumab plus enfortumab vedotin-ejfv prior to surgery followed by adjuvant durvalumab, radical cystectomy alone, or an additional investigational combination regimen.
According to the FDA, the combination treatment demonstrated statistically significant improvements in both event-free and overall survival compared with radical cystectomy alone. Median event-free survival was not reached in the combination arm vs. 12.1 months with surgery alone. Median overall survival was not reached in either group, although the combination demonstrated a statistically significant survival advantage.
Common adverse reactions and laboratory abnormalities occurring in more than 20% of patients included increased aspartate aminotransferase and alanine aminotransferase levels, decreased hemoglobin, rash, pruritus, urinary tract infection, fatigue, diarrhea, nausea, and peripheral neuropathy.
Among patients weighing at least 30 kg, the recommended regimen includes durvalumab 1,500 mg every 3 weeks with neoadjuvant enfortumab vedotin-ejfv 1.25 mg/kg on days 1 and 8 for 3 presurgical cycles, followed by single-agent durvalumab 1,500 mg every 4 weeks for up to 9 postoperative cycles. Among patients weighing less than 30 kg, the recommended durvalumab dose is 20 mg/kg on the same schedule.
The application received priority review and was approved 6 weeks ahead of the FDA's goal date under Project Orbis.
Source: FDA
