Perioperative enfortumab vedotin-pembrolizumab, gemcitabine-cisplatin-durvalumab, and dose-dense MVAC in cisplatin-eligible muscle-invasive bladder cancer: A benefit-risk Bayesian network meta-analysis.

Authors

José Daniel Subiela, Daniel A González-Padilla, Pietro Scilipoti, Aleksander Slusarczyk, Renate Pichler, Félix Guerrero-Ramos, Alberto Artiles-Medina, Jorge Caño-Velasco, Júlia Aumatell, Wojciech Krajewski, Laura S Mertens, Jeremy Yuen-Chun Teoh, Roberto Contieri, Brigida Anna Maiorano, Francesco Claps, Francesco Del Giudice, David D'Andrea, Pablo Gajate, Patricia Guerrero, Andrea Gallioli, Felipe Villacampa, Eduardo Albers Acosta, Fernando Lozano, Albert Carrion, Luca Afferi, Luis Crespo, Gautier Marcq, Francesco Soria, Marco Moschini, Elisabeth Grobet-Jeandin, Simone Albisinni, Mario Alvarez-Maestro, Luis San-José Manso, Victoria Gomez Dos Santos, Morgan Roupret, Francisco Javier Burgos Revilla, Benjamin Pradere, Oscar Buisan, Young Academic Urologist (YAU) Urothelial Carcinoma Working Group

Published in

Urologic oncology. Sep 22, 2026. Epub Sep 22, 2026.

Abstract

To compare the efficacy and safety of three perioperative regimens for cisplatin-eligible muscle-invasive bladder cancer (MIBC); enfortumab vedotin plus pembrolizumab (EV + P), gemcitabine-cisplatin plus durvalumab (GC + Durva), and dose-dense MVAC (dd-MVAC), in the absence of head-to-head trials, using a Bayesian network meta-analysis (NMA). A systematic search through March 2026 identified phase III trials comparing perioperative regimens against GC in cisplatin-eligible MIBC. The primary analysis was a Bayesian NMA of event-free survival (EFS), overall survival (OS), and pathological complete response (pCR), with SUCRA rankings; risk of bias used RoB-2. Three trials (EV-304, NIAGARA, VESPER; 2,364 patients) formed a star-shaped network vs. GC, all regimens improved EFS-EV + P (Hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.41-0.70), GC + Durva (0.68, 0.56-0.82), dd-MVAC (0.74, 0.55-0.99), and OS, EV + P (0.65, 0.48-0.89), GC + Durva (0.75, 0.60-0.93), dd-MVAC (0.71, 0.52-0.97). EV + P ranked first across all endpoints (SUCRA: EFS 96%, OS 81%, pCR > 99%). Indirect comparisons between experimental regimens were non-significant for survival; only pCR favored EV + P over GC + Durva (odds ratio [OR] 1.7, P < 0.01) and dd-MVAC (OR 2.0, P < 0.01). GC + Durva showed no excess Grade ≥3 toxicity over GC (41% vs. 41%). This NMA provides the first quantitative benefit-risk framework integrating efficacy ranking, toxicity, and subgroup heterogeneity for these regimens. EV + P had the highest probability of improving EFS, OS, and pCR, with GC + Durva ranking second; although directionally consistent with each trial, the magnitude, ranking, and subgroup heterogeneity could not be quantified without indirect synthesis. GC + Durva offered the most favorable benefit-risk profile. Prospective head-to-head trials remain an unmet need.

PMID:
42881094
Bibliographic data and abstract were imported from PubMed on 16 Oct 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.