metastatic urothelial carcinoma (3.5-year update)¶

Abstract: 4507 · Session: Genitourinary Cancer — Kidney and Bladder (Oral Abstract Session), 2026 ASCO Annual Meeting, Chicago · Presenter: Thomas Powles, MD, PhD (Barts Cancer Centre, Queen Mary University of London) · Embargo: per ASCO Annual Meeting (May 29 – Jun 2, 2026)

At a glance¶

Sponsor: Astellas / Pfizer (Seagen) and Merck — co-development of enfortumab vedotin (Padcev) and pembrolizumab (Keytruda)
PI / presenter: Thomas Powles, MD, PhD — Barts Cancer Centre, Queen Mary University of London
NCT ID: NCT04223856
Phase: 3
Design: Open-label, randomized 1:1; EV + pembrolizumab vs platinum-based chemotherapy (gemcitabine + cisplatin or carboplatin)
N: 886 (EV+P n = 442; chemo n = 444)
Primary endpoint(s): Overall survival (OS) and progression-free survival (PFS)
Comparator: Platinum-based chemotherapy
Indication: Previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC)
Line: First-line (1L)

Headline result¶

At a median follow-up of 42.8 months (3.5 years), EV + pembrolizumab continued to deliver a roughly doubled overall survival over chemotherapy in the ITT population: median OS 33.6 months (95% CI, 26.6–39.8) vs 15.9 months (95% CI, 13.6–18.3), with a 42-month OS rate of 44.0% vs 24.6% (HR 0.53; 95% CI, 0.45–0.63). Confirmed complete responses occurred in 30.4% of the EV+P arm (n = 133) vs 14.5% with chemotherapy (n = 64); among confirmed responders, CR rates were 45.1% vs 32.8%. CRs were durable: patients achieving CR with EV+P had a 42-month OS rate of 83.6% with median OS not yet reached, and the OS benefit held even within the CR subgroup (HR 0.36; 95% CI, 0.20–0.68). 66.2% of EV+P CRs first achieved a partial response before converting to CR.

Mechanism / class¶

Enfortumab vedotin is a Nectin-4–directed antibody-drug conjugate delivering the microtubule inhibitor MMAE; pembrolizumab is an anti–PD-1 immune checkpoint inhibitor. The combination won full FDA approval in December 2023 for 1L la/mUC on the basis of the original EV-302 readout, displacing platinum chemotherapy as the standard of care regardless of cisplatin eligibility.

Discussant takeaway¶

Powles framed the long-term data as confirming a "transformative" and durable survival benefit, with the responder and CR analyses underscoring that deep, durable responses translate into extended survival.

Practice-changing?¶

No — confirmatory. EV + pembrolizumab is already the established 1L standard for la/mUC since the original EV-302 results; this 3.5-year update reinforces the durability of the survival advantage rather than altering practice.

Cross-links¶

Other ASCO 2026 trials: (other GU / urothelial abstracts in ./)

Sources¶

ASCO Meeting Library / J Clin Oncol 2026;44(suppl 16):4507 (abstract 4507)
OncLive: https://www.onclive.com/view/updated-ev-302-data-reinforce-enfortumab-vedotin-combo-s-durability-in-urothelial-carcinoma-at-asco-2026
Urology Times: https://www.urologytimes.com/view/ev-p-maintains-os-benefit-at-3-5-years-in-metastatic-uc
CancerNetwork: https://www.cancernetwork.com/view/enfortumab-vedotin-pembrolizumab-shows-long-term-survival-benefit-in-1l-urothelial-carcinoma
OncoDaily: https://oncodaily.com/genitourinary-oncology/ev-302-at-asco-2026
AJMC: https://www.ajmc.com/view/powles-highlights-transformative-benefit-of-ev-plus-pembro-while-sharing-long-term-data-for-ev-302