Journal article
Genomic Biomarkers Associated with Enfortumab Vedotin Outcomes for Patients with Advanced Urothelial Carcinoma: Analysis of UNITE Study Data
European urology oncology, Vol.8(2), pp.258-262
04/2025
DOI: 10.1016/j.euo.2024.12.006
PMID: 39709257
Abstract
Genomic biomarkers from next-generation sequencing panels may help in identifying patients with advanced urothelial cancer who are more or less likely to experience a benefit from enfortumab vedotin. Robust validation in external cohorts and further exploration of these hypothesis-generating findings are needed before clinical application.
Enfortumab vedotin (EV) is used as monotherapy or combined with pembrolizumab in advanced urothelial carcinoma (aUC), but biomarker data associated with EV outcomes are limited. We identified 170 patients in the UNITE study who received EV monotherapy and had molecular biomarker data available. Outcomes for groups with and without a particular biomarker were compared using logistic regression (unadjusted) for the objective response rate (ORR), and a log-rank test and Cox proportional-hazard models (CPHMs) for progression-free survival (PFS) and overall survival (OS) from EV initiation. Molecular biomarkers were also evaluated in separate multivariable analyses using CPHMs that accounted for clinical characteristics. Median patient age was 70 yr; 78% of the cohort were male and 65% had pure UC histology. Median PFS was shorter for patients with CDKN2A alterations (4.6 vs 6 mo; p = 0.024) and for patients with CDKN2B alterations (4.4 vs 6 mo; p = 0.008). Median OS was longer for patients with high tumor mutational burden (13.6 vs 8.3 mo; p = 0.014). ORR was higher for patients with TSC1 alterations (87% vs 51%; p = 0.018). In multivariable analyses, CDKN2A and CDKN2B alterations were associated with inferior median PFS. This multi-institutional retrospective study of patients with aUC identified potential biomarkers associated with EV monotherapy outcomes that should be further investigated.
We investigated genetic changes in urinary tract tumors that might be associated with response to enfortumab vedotin (EV) treatment in patients with advanced disease. Survival after EV treatment was longer for tumors with a higher number of mutations than for tumors with fewer mutations. However, mutations in two genes (CDKN2A and CDKN2B) were associated with worse outcomes after EV treatment. These findings will not affect current clinical practice.
Details
- Title: Subtitle
- Genomic Biomarkers Associated with Enfortumab Vedotin Outcomes for Patients with Advanced Urothelial Carcinoma: Analysis of UNITE Study Data
- Creators
- Tanya Jindal - University of California, San FranciscoCindy Jiang - The University of Texas MD Anderson Cancer CenterOmar Alhalabi - The University of Texas MD Anderson Cancer CenterAmanda Nizam - Cleveland ClinicCharles Nguyen - University of MichiganRafee Talukder - University of WashingtonDimitra Bakaloudi - University of WashingtonMatthew Davidsohn - Dana-Farber Cancer InstituteDory Freeman - Dana-Farber Cancer InstituteMichael Glover - Stanford UniversityAli Raza Khaki - Stanford UniversitySean Evans - Emory UniversityEmily Lemke - Medical College of WisconsinRohit Bose - UCSF Helen Diller Family Comprehensive Cancer CenterWoogwang Sim - UCSF Helen Diller Family Comprehensive Cancer CenterCameron Pywell - University of Alabama at BirminghamArnab Basu - University of Alabama at BirminghamDeepak Kilari - Medical College of WisconsinPedro C. Barata - University Hospitals Seidman Cancer CenterMehmet A. Bilen - Emory UniversityYousef Zakharia - University of IowaMatthew I. Milowsky - University of North Carolina at Chapel HillSumit A. Shah - Stanford UniversityJoaquim Bellmunt - Dana-Farber Cancer InstitutePetros Grivas - University of WashingtonHamid Emamekhoo - University of Wisconsin–MadisonNancy B. Davis - Vanderbilt UniversityShilpa Gupta - Cleveland ClinicChristopher Hoimes - Duke UniversityMatthew T. Campbell - The University of Texas MD Anderson Cancer CenterAjjai Alva - University of MichiganVadim S. Koshkin - University of California, San Francisco
- Resource Type
- Journal article
- Publication Details
- European urology oncology, Vol.8(2), pp.258-262
- DOI
- 10.1016/j.euo.2024.12.006
- PMID
- 39709257
- NLM abbreviation
- Eur Urol Oncol
- ISSN
- 2588-9311
- eISSN
- 2588-9311
- Publisher
- Elsevier B.V
- Grant note
- PureTechBristol-Myers SquibbMirati TherapeuticsGenentechJanssen
Health, PureTech, G1 Therapeutics, Aadi Biosciences, CG Oncology, Strata Oncology, ImmunityBio, Asieris Pharmaceuticals, and AbbVie; and institutional research funding from Pfizer, Bristol-Myers Squibb, MSD, QED Therapeutics, GlaxoSmithKline, Mirati Therapeutics, EMD Serono, G1 Therapeutics, Gilead Sciences, Acrivon Therapeutics, ALX Oncology, and Genentech. Ali Raza Khaki reports institutional research funding from Pfizer, Janssen, Acrivon Therapeutics, and 23andMe; an uncompensated consulting role for Janssen; and an uncompensated advisory board role for Pfizer/Astellas. The remaining authors have nothing to disclose.
- Language
- English
- Electronic publication date
- 12/20/2024
- Date published
- 04/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984758188502771
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