Design: Phase 3, open-label, three-arm randomised trial (VOLGA)
Population: 695 patients with cisplatin-ineligible muscle-invasive bladder cancer
Primary outcome: Event-free survival
Effect: 24-month EFS 63.5% vs 45.1%; HR 0.51 (95% CI 0.38 to 0.67); OS HR 0.58

VOLGA was an open-label phase 3 trial in 695 patients with muscle-invasive bladder cancer who were ineligible for, or declined, cisplatin-based chemotherapy. Patients received three cycles of neoadjuvant durvalumab plus enfortumab vedotin, then cystectomy and adjuvant durvalumab; the same with tremelimumab added; or cystectomy alone.

At 24 months, event-free survival was 63.5% with durvalumab–enfortumab vedotin against 45.1% with surgery alone (hazard ratio 0.51, 95% CI 0.38 to 0.67), and overall survival 78.4% against 69.4% (0.58, 0.40 to 0.83). Adding tremelimumab also improved event-free survival (60.1%; hazard ratio 0.61) but with more toxicity. Grade 3 or higher adverse events occurred in 71.1% of the durvalumab–enfortumab vedotin group, of which 30.7% were treatment-related, against 50.2% with surgery alone.

This gives cisplatin-ineligible patients — often older, with renal impairment — a perioperative option with an overall survival gain, where until now surgery alone was the usual route. Cost and access to enfortumab vedotin will limit uptake in India, and the trial was industry-funded and open-label.

Assess cisplatin eligibility formally in every patient with muscle-invasive bladder cancer.
Discuss perioperative durvalumab with enfortumab vedotin for cisplatin-ineligible patients fit for cystectomy.
Monitor for skin toxicity, neuropathy and hyperglycaemia with enfortumab vedotin.
Weigh the added toxicity of tremelimumab, which was not compared directly with the doublet.

Why it matters

Patients who cannot have cisplatin have had few perioperative options with a survival benefit.

The statistics, in plain English

An event-free survival hazard ratio of 0.51 means about half the rate of recurrence, progression or death at any point. The overall survival gain (69.4% to 78.4% at two years) is about 9 more people alive per 100 treated. The two durvalumab arms were each compared with surgery, not with each other.