VOLGA: Durvalumab plus enfortumab vedotin improves EFS, OS in MIBC

News | Articles | October 24, 2026 Perioperative durvalumab (Imfinzi) plus neoadjuvant enfortumab vedotin-ejfv (Padcev) cut the risk of EFS events by 49% and death by 42% in cisplatin-ineligible MIBC. Perioperative durvalumab (Imfinzi) plus neoadjuvant enfortumab vedotin-ejfv (Padcev) significantly improved event-free survival (EFS) and overall survival (OS) in patients with muscle-invasive bladder cancer (MIBC) ineligible for or refusing cisplatin, according to interim phase 3 VOLGA (NCT04960709) results.

1,2 Thomas Powles, MD, of Barts Cancer Institute, Queen Mary University of London, United Kingdom, presented the late-breaking data at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid, Spain.1 The data were also published in the New England Journal of Medicine.

2 The 24-month EFS rate reached 64% with the combination versus 45% in the control arm.1 Radical cystectomy (RC) alone carries high recurrence rates and a poor prognosis in MIBC, according to the investigators.1 Durvalumab was the first immunotherapy approved for perioperative MIBC treatment in combination with neoadjuvant chemotherapy and RC, and perioperative enfortumab vedotin plus pembrolizumab strategies have further expanded options.1 VOLGA evaluated durvalumab, with or without tremelimumab (Imjudo), plus enfortumab vedotin in the cisplatin-ineligible or cisplatin-refusing population.1 The open-label VOLGA trial (NCT04960709) randomly assigned 695 patients with cT2-T4aN0/1M0 or cT1N1M0 MIBC in a 1:1:1 ratio.

1-3 Arms included durvalumab plus enfortumab vedotin (D+EV; n = 233), durvalumab plus tremelimumab and enfortumab vedotin (D+T+EV; n = 233), and control (n = 229).1 Dual primary end points were EFS by blinded independent central review for each experimental arm vs control, with OS as the key secondary end point.1 Patients in the experimental arms received 3 neoadjuvant cycles of durvalumab 1500 mg and enfortumab vedotin 1.25 mg/kg every 3 weeks, followed by RC and nine adjuvant cycles of durvalumab every 4 weeks.1 The triplet arm added tremelimumab 75 mg for 2 neoadjuvant cycles and 1 adjuvant cycle.1 Control patients proceeded directly to RC, followed by observation or locally approved adjuvant therapy.1 At a median EFS follow-up of 22.9 months, D+EV reduced the risk of an EFS event by 49% vs control (HR, 0.51; 95% CI, 0.38-0.67; P < .0001).1 Median EFS was not reached with D+EV versus 12.1 months with control.1 D+T+EV also met its EFS end point (HR, 0.61; 95% CI, 0.47-0.80; P = .0004), with a 24-month EFS rate of 60% vs 45%.1 Overall survival, pathologic complete response, and safety with perioperative durvalumab plus enfortumab vedotin D+EV significantly improved OS vs control (HR, 0.58; 95% CI, 0.40-0.83; P = .0027), with 24-month OS rates of 78% and 69%, respectively.1 OS with D+T+EV did not reach statistical significance at this interim analysis (HR, 0.77; 95% CI, 0.54-1.07; P = .1230), and follow-up is ongoing.1 The investigators reported EFS and OS benefits with D+EV were consistent across prespecified subgroups.1 Per local pathology review, pathologic complete response (pCR) occurred in 45% (105/233) of patients receiving D+EV vs 10% (22/229) of control patients (risk ratio, 4.7; 95% CI, 3.1-7.3).1 Central independent review showed pCR rates of 40% (94/233) and 8% (19/229), respectively.1 In an exploratory analysis, 60% (52/87) of D+EV patients with baseline circulating tumor DNA (ctDNA) achieved ctDNA clearance before RC.1 The 24-month EFS rate was 81% among patients with clearance vs 55% among those with persistently positive ctDNA.1 Grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 30% of patients receiving D+EV and 42% of patients receiving D+T+EV.1 Any-grade immune-mediated AEs occurred in 33% and 48%, respectively, and possibly treatment-related deaths occurred in 1 patient (0.4%) and 5 patients (2%).1 The most common any-grade AEs with D+EV were pruritus (44%), urinary tract infection (36%), and anemia (32%).1 Peripheral neuropathy occurred in 18% of D+EV patients, mostly grade 1.1 Patient-reported global health status and quality of life were maintained after surgery in the D+EV arm, per EORTC QLQ-C30 data.1 The investigators concluded VOLGA supports perioperative durvalumab plus 3 cycles of neoadjuvant enfortumab vedotin as a potential new standard of care for patients with MIBC ineligible for or refusing cisplatin.1 RC was completed in 85% of D+EV patients, 79% of D+T+EV patients, and 78% of control patients.1 The protocol recommended surgery within 56 days of the last neoadjuvant dose, and AEs delayed surgery in 4% of D+EV patients.1 REFERENCES 1.

Powles T, Grande E, Simone G, et al. Perioperative durvalumab with or without tremelimumab plus neoadjuvant enfortumab vedotin in muscle-invasive bladder cancer: results from the phase 3 VOLGA trial. Presented at: European Society for Medical Oncology Congress 2026; October 23-27, 2026, Madrid, Spain.

Abstract LBA2. https://cslide.ctimeetingtech.com/esmo2026/attendee/confcal/show/session/346 2. Powles T, Grande E, Simone G, et al. Durvalumab, tremelimumab, and enfortumab vedotin in muscle-invasive bladder cancer.

N Engl J Med. Published online October 24, 2026. Accessed October 24, 2026. https://www.nejm.org/doi/full/10.1056/NEJMoa2608323?query=featured_home 3.

VOLGA. ClinicalTrials.gov identifier: NCT04960709. Accessed October 24, 2026.

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