The standard of care continues to evolve for patients (pts) with muscle-invasive bladder cancer (MIBC). We evaluated if neoadjuvant durvalumab (D) ± tremelimumab (T) plus enfortumab vedotin (EV) followed by radical cystectomy (RC) and adjuvant D±T would be an effective option.
VOLGA (NCT04960709), a phase 3, randomised, open-label trial, enrolled pts with MIBC (cT2-T4aN0/1M0 or cT1N1M0) ineligible for or who refused treatment (tx) with cisplatin and were planned for RC. Pts were randomised 1:1:1 to D+EV, D+T+EV, or control. D+EV and D+T+EV arms: perioperative D±T (neoadjuvant: 3 cycles of D, 2 cycles of T; adjuvant: 9 cycles of D, 1 cycle of T) and 3 cycles of neoadjuvant EV; RC was completed after neoadjuvant tx. Control arm: RC and observation or locally approved adjuvant tx. Dual primary endpoints were event-free survival (EFS): D+EV vs control and D+T+EV vs control. Overall survival (OS) was the key secondary endpoint. Safety was also assessed. Here we present results from a pre-planned interim analysis (data cutoff: 02 Mar 2026).
Overall, 233, 233, and 229 pts were randomised to the D+EV, D+T+EV, and control arms, respectively. RC was completed in 85% (D+EV), 79% (D+T+EV), and 78% (control) of pts; and 55% (D+EV) and 42% (D+T+EV) completed adjuvant tx. Median EFS follow-up was 22.9 mo. D+EV showed significant improvements in EFS (HR 0.51 [95% CI, 0.38–0.67], P<0.0001; 24-mo rate 64% vs 45%) and OS (HR 0.58 [95% CI, 0.40–0.83], P=0.0027; 24-mo rate 78% vs 69%) vs control. D+T+EV also showed a significant improvement in EFS vs control (HR 0.61 [95% CI, 0.47–0.80], P=0.0004; 24-mo rate 60% vs 45%) but did not meet significance for OS; follow-up is ongoing. Pathological complete response per local review was observed in 45% (95% CI, 38.6–51.7) of pts in the D+EV arm and 10% (95% CI, 6.1–14.2) in the control arm. In the D+EV and D+T+EV arms, max. Grade 3/4 tx-related adverse events occurred in 30% and 42% of pts, respectively. ctDNA results will also be presented.
Dual primary endpoints of EFS were met. Perioperative D plus 3 cycles of neoadjuvant EV also demonstrated a significant improvement in OS vs control. Safety profiles were consistent with those of the individual agents.
NCT04960709; EudraCT 2023-507342-84-00.