Perioperative treatment with AstraZeneca’s Imfinzi (durvalumab) plus neoadjuvant Padcev (enfortumab vedotin) cut the risk of disease progression, recurrence, not undergoing surgery or death by 49 percent against surgery-based standard care in muscle-invasive bladder cancer, in the Phase 3 VOLGA trial presented at ESMO on October 24 and published simultaneously in The New England Journal of Medicine. The event-free survival hazard ratio was 0.51 (95 percent confidence interval 0.38 to 0.67, p below 0.0001), median event-free survival was not yet reached against 12.1 months on the comparator, and 64 percent of combination patients were alive and event-free at two years against 45 percent. The risk of death fell by 42 percent, the key secondary endpoint.
VOLGA randomised 695 patients who were ineligible for, or had refused, cisplatin chemotherapy, across three arms: Imfinzi plus Padcev, Imfinzi plus Imjudo plus Padcev, and a control arm of radical cystectomy with or without approved adjuvant treatment. The figures above are for the two-drug arm. More than three quarters of patients on that arm were still alive two years after treatment, AstraZeneca said, with a manageable safety profile.
The competitive comparison is the story. Merck’s Keytruda plus Padcev set the current perioperative standard in a similar cisplatin-ineligible population with a 50 percent reduction in the risk of death in the EV-303 trial. VOLGA’s 42 percent is smaller on a cross-trial comparison, which Fierce Pharma noted has its own flaws, but AstraZeneca achieved it with less Padcev: three cycles before surgery only, against nine cycles before and after surgery in the Keytruda regimen, and 12 cycles of Imfinzi in total. AstraZeneca’s oncology research chief Susan Galbraith described the regimen to Fierce as a patient-centric option that can challenge the current standard of care.
Nothing here is an approval yet. VOLGA is an interim analysis in a population defined by cisplatin ineligibility, and the three-drug arm’s separate readout, plus regulatory filings, will decide whether Imfinzi gains a perioperative bladder label on this regimen.