---
title: "Perioperative enfortumab vedotin plus pembrolizumab improves outcomes in cisplatin-eligible MIBC"
id: "nature-reviews-clinical-oncology-0-benefit-from-perioperative-enfortumab-vedotin-pembrolizumab-in-cisplatin"
canonical_url: "https://medichelpline.com/clinical-feed/nature-reviews-clinical-oncology-0-benefit-from-perioperative-enfortumab-vedotin-pembrolizumab-in-cisplatin"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "Nature Reviews Clinical Oncology"
source_url: "https://www.nature.com/articles/s41571-026-01195-2"
published_at: "2026-08-04T12:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Perioperative enfortumab vedotin plus pembrolizumab improves outcomes in cisplatin-eligible MIBC
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/nature-reviews-clinical-oncology-0-benefit-from-perioperative-enfortumab-vedotin-pembrolizumab-in-cisplatin
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** Nature Reviews Clinical Oncology
- **Source URL:** [Original Journal Publication](https://www.nature.com/articles/s41571-026-01195-2)
- **Published At:** 2026-08-04T12:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- Standard of care for resectable **muscle-invasive bladder cancer (MIBC)** has been neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy. - The phase III KEYNOTE-905/EV-303 trial previously showed benefit of perioperative **enfortumab vedotin (EV)** plus **pembrolizumab** for patients who are cisplatin-ineligible or who decline cisplatin. - The phase III KEYNOTE-B15/EV-304 trial randomized 808 cisplatin-eligible patients 1:1 to perioperative EV–pembrolizumab versus standard neoadjuvant cisplatin–gemcitabine before surgery. - The EV–pembrolizumab arm received four cycles of combination therapy preoperatively, followed by radical cystectomy with pelvic lymph node dissection, then adjuvant EV (five cycles) and pembrolizumab (thirteen cycles). - The chemotherapy arm received four cycles of neoadjuvant cisplatin–gemcitabine before surgery. - A protocol amendment permitted adjuvant **nivolumab** in the chemotherapy group when clinically indicated; however, only 7.8% of patients in that group received nivolumab. - The primary end point of KEYNOTE-B15/EV-304 was **event-free survival (EFS)**. - According to a research highlight, perioperative EV–pembrolizumab improved outcomes compared with neoadjuvant cisplatin–gemcitabine in cisplatin-eligible patients with MIBC. - The report references the original phase III trial publication in the New England Journal of Medicine for detailed results. - Details such as specific effect sizes, hazard ratios, absolute event rates, adverse-event profiles and long-term follow-up were not reported in the source highlight and require consultation of the primary trial report for comprehensive data.
## Clinical Analysis & Structured Key Points
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[nature](https://www.nature.com/) 2. [nature reviews clinical oncology](https://www.nature.com/nrclinonc) 3. [research highlights](https://www.nature.com/nrclinonc/articles?type=research-highlight) 4. article * Research Highlight * Published: 04 August 2026 Urological cancer # Benefit from perioperative enfortumab vedotin–pembrolizumab in cisplatin-eligible MIBC * [Diana Romero](https://www.nature.com/articles/s41571-026-01195-2#auth-Diana-Romero-Aff1)[1](https://www.nature.com/articles/s41571-026-01195-2#Aff1) [_Nature Reviews Clinical Oncology_](https://www.nature.com/nrclinonc) (2026) [Cite this article](https://www.nature.com/articles/s41571-026-01195-2#citeas) [ Save article ](https://www.nature.com/articles/s41571-026-01195-2/save-research?_csrf=BBYPRnPx03Jsc0Oa9z5M6EivG_97K-GE) [ View saved research ](https://www.nature.com/saved-research) Neoadjuvant cisplatin-based chemotherapy followed by cystectomy is the established standard of care (SOC) for patients with resectable muscle-invasive bladder cancer (MIBC). More recently, the phase III KEYNOTE-905/EV-303 trial showed that those who are ineligible for or decline cisplatin-based regimens can derive substantial benefit from perioperative treatment with the nectin 4-targeted antibody–drug conjugate enfortumab vedotin (EV) plus the anti-PD-1 antibody pembrolizumab. Now, data from the phase III KEYNOTE-B15/EV-304 trial show that perioperative EV–pembrolizumab also improves the outcomes of patients with MIBC eligible for SOC therapy. A total of 808 patients were randomly allocated (1:1) to receive perioperative EV–pembrolizumab (4 cycles before radical cystectomy with pelvic lymph node dissection followed by 5 cycles of EV and 13 cycles of pembrolizumab) versus neoadjuvant chemotherapy (4 cycles of cisplatin–gemcitabine before surgery). A protocol amendment allowed adjuvant treatment with the anti-PD-1 antibody nivolumab in the chemotherapy group when clinically indicated, although only 7.8% received such treatment. Event-free survival (EFS) was the primary end point. 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D. et al. Enfortumab vedotin and pembrolizumab in cisplatin-eligible bladder cancer. _N. Engl. J. Med._ **395** , 338–348 (2026) [Article](https://doi.org/10.1056%2FNEJMoa2601486) [CAS](https://www.nature.com/articles/cas-redirect/1:CAS:528:DC%2BB28XhvFWiur7F) [PubMed](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=42485627) [ Google Scholar](http://scholar.google.com/scholar_lookup?&title=Enfortumab%20vedotin%20and%20pembrolizumab%20in%20cisplatin-eligible%20bladder%20cancer&journal=N.%20Engl.%20J.%20Med.&doi=10.1056%2FNEJMoa2601486&volume=395&pages=338-348&publication_year=2026&author=Galsky%2CMD) [Download references](https://citation-needed.springer.com/v2/references/10.1038/s41571-026-01195-2?format=refman&flavour=references) ## Author information ### Authors and Affiliations 1. Nature Reviews Clinical Oncology Diana Romero Authors 1. 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