Durvalumab, Tremelimumab, and Enfortumab Vedotin in Muscle-Invasive Bladder Cancer

The standard of care for patients with muscle-invasive bladder cancer continues to evolve.

By Powles, Grande, Simone +23The New England journal of medicineOct 24, 2026

Score█████░░░░░5.2

Key numbers

95% confidence interval
95% CI
78.4% and 69.4%

VerdictA leading story on any desk.

Read the original

Abstract

Background The standard of care for patients with muscle-invasive bladder cancer continues to evolve. Whether perioperative durvalumab, with or without tremelimumab, plus neoadjuvant enfortumab vedotin is effective in such patients is unknown. Methods In this phase 3 open-label trial, we randomly assigned, in a 1:1:1 ratio, patients with muscle-invasive bladder cancer who were ineligible for or declined cisplatin-based chemotherapy to receive neoadjuvant durvalumab-enfortumab vedotin every 3 weeks for three cycles, followed by radical cystectomy and then adjuvant durvalumab every 4 weeks for nine cycles; neoadjuvant durvalumab-tremelimumab-enfortumab vedotin (tremelimumab for two cycles only), radical cystectomy, and adjuvant durvalumab-tremelimumab (tremelimumab for one cycle only); or radical cystectomy alone (control). The dual primary end points were event-free survival in each of the two durvalumab groups as compared with that in the control group. The two durvalumab groups were not compared with each other. The key secondary end point was overall survival. Results In total, 233 patients were assigned to the durvalumab-enfortumab vedotin group, 233 to the durvalumab-tremelimumab-enfortumab vedotin group, and 229 to the control group. Estimated event-free survival at 24 months was 63.5% (95% confidence interval [CI], 56.5 to 69.7) with durvalumab-enfortumab vedotin and 45.1% (95% CI, 38.2 to 51.8) with control (hazard ratio for an event or death, 0.51; 95% CI, 0.38 to 0.67; P<0.001); estimated overall survival at 24 months was 78.4% and 69.4%, respectively (hazard ratio for death, 0.58; 95% CI, 0.40 to 0.83; P = 0.003). Estimated event-free survival at 24 months was 60.1% (95% CI, 53.2 to 66.2) with durvalumab-tremelimumab-enfortumab vedotin (hazard ratio for an event or death vs. control, 0.61; 95% CI, 0.47 to 0.80; P<0.001). Grade 3 or higher adverse events occurred in 71.1% of patients in the durvalumab-enfortumab vedotin group (treatment-related, 30.7%), in 79.5% of those in the durvalumab-tremelimumab-enfortumab vedotin group (treatment-related, 44.5%), and in 50.2% of those in the control group. Conclusions Perioperative durvalumab with or without tremelimumab plus three cycles of neoadjuvant enfortumab vedotin resulted in significantly better event-free survival outcomes than surgery alone. Perioperative durvalumab plus enfortumab vedotin led to significantly better overall survival outcomes than surgery alone. Grade 3 or higher adverse events of any cause were noted in more than half the patients in the durvalumab groups. (Funded by AstraZeneca; VOLGA ClinicalTrials.gov number, NCT04960709; EudraCT number, 2020-005452-38.).

Thomas Powles, Enrique Grande, Giuseppe Simone, Alfonso Gómez de Liaño, Marco Maruzzo, Pedro Isaacsson Velho, Eiji Kikuchi, Toan Quang Vu, Lazar Popovic, Timuçin Çil, Gwenaelle Gravis, Robert Radkowski, Luis Raúl Novelo Hernández, Hernán Javier Cutuli, Aristotelis Bamias, Thomas Bauernhofer, Michel Pavic, Yoon Ji Choi, Chao-Hsiang Chang, Hiroshi Kitamura, Jonathan E Rosenberg, Jacqui Rowbottom, Svetlana Ho, Ashok Gupta, Alexandra Drakaki, VOLGA Investigators

The editor's rubric

Heuristic review

Leverage2 / 5: Reusable within one subfield (a technique, dataset, or protocol a few groups will adopt).; 10% of this desk’s rubric
Magnitude3 / 5: Large gain: roughly 2x, or a clear new state of the art on a hard, unsaturated problem.; 20% of this desk’s rubric
Evidence5 / 5: Definitive: phase 3 randomized evidence on hard endpoints, multi-lab replication, or community verification at scale.; 32% of this desk’s rubric
Novelty3 / 5: A genuinely new approach to an open problem.; 8% of this desk’s rubric
Trajectory2 / 5: Some room to improve with obvious engineering.; 5% of this desk’s rubric
Stakes3 / 5: Meaningful benefit to many people within a few years.; 25% of this desk’s rubric

Dimension	Level	Weight	What that level means
Leverage	██░░░2/5	10%	Reusable within one subfield (a technique, dataset, or protocol a few groups will adopt).
Magnitude	███░░3/5	20%	Large gain: roughly 2x, or a clear new state of the art on a hard, unsaturated problem.
Evidence	█████5/5	32%	Definitive: phase 3 randomized evidence on hard endpoints, multi-lab replication, or community verification at scale.
Novelty	███░░3/5	8%	A genuinely new approach to an open problem.
Trajectory	██░░░2/5	5%	Some room to improve with obvious engineering.
Stakes	███░░3/5	25%	Meaningful benefit to many people within a few years.

Editor’s rationale

Heuristic triage from title and abstract text only, not a reading of the paper. Cues found: gains (efficacy); design (randomized, placebo-controlled, phase 3); verification (confidence interval, p-value); stakes (mortality, major disease, prevention or cure).

How the score was computed

rank-2026-10-18

Score█████░░░░░5.2

Score = 10 × (80% × adjusted merit / 10 + 10% × attention + 10% × freshness)

Desks place stronger verdicts first, then use this score to order work within the same verdict.

Merit: 7.0 / 10; Weighted rubric, evidence-gated.
Adjusted merit: 5.5 / 10; Shrunk toward the desk prior by editor confidence (50%).
Attention: 0%; Citations, upvotes, points, mentions.
Freshness: 80%; Half-life decay since publication.

Citations0 (reference 20, via openalex, Oct 27, 2026, 06:17 UTC)

The record

Reviewed by heuristic-v10 on Oct 27, 2026, 06:17 UTC. Paper type: clinical.
Categories: Journal Article
BRIEF, No.2 in the Medicine edition of October 27, 2026.