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