Journal article
Treatment-Related Adverse Events and Associated Outcomes in Patients With Advanced Urothelial Carcinoma Treated With Enfortumab Vedotin: Analysis of the UNITE Study
Cancer medicine (Malden, MA), Vol.14(19), e71284
10/01/2025
DOI: 10.1002/cam4.71284
PMCID: PMC12486332
PMID: 41031719
Abstract
Enfortumab vedotin-ejfv (EV), an antibody-drug conjugate approved for advanced urothelial carcinoma (aUC), has limited real-world safety data and no validated predictive biomarkers. Retrospective studies suggest higher objective response rates (ORR) among patients developing EV-related dermatologic toxicities, but survival implications remain unclear. This analysis assessed the safety of EV monotherapy and the impact of dermatologic and neurologic toxicities on efficacy outcomes in a multi-institutional cohort.INTRODUCTIONEnfortumab vedotin-ejfv (EV), an antibody-drug conjugate approved for advanced urothelial carcinoma (aUC), has limited real-world safety data and no validated predictive biomarkers. Retrospective studies suggest higher objective response rates (ORR) among patients developing EV-related dermatologic toxicities, but survival implications remain unclear. This analysis assessed the safety of EV monotherapy and the impact of dermatologic and neurologic toxicities on efficacy outcomes in a multi-institutional cohort.UNITE is a multicenter, retrospective study across 16 US sites of patients with aUC treated with targeted agents, including EV. Primary endpoints were the incidence of EV treatment-related adverse events (TRAEs, any grade) and TRAE-related treatment modifications. Secondary endpoints included a comparison of ORR, progression-free survival (PFS), and overall survival (OS) between patients with and without dermatologic toxicities and neuropathy. To reduce immortal time bias, Cox regression models incorporated TRAEs as time-dependent covariates to adjust for EV treatment duration as well as Eastern Cooperative Oncology Group performance status (ECOG PS), hemoglobin, and liver metastases.MATERIALS AND METHODSUNITE is a multicenter, retrospective study across 16 US sites of patients with aUC treated with targeted agents, including EV. Primary endpoints were the incidence of EV treatment-related adverse events (TRAEs, any grade) and TRAE-related treatment modifications. Secondary endpoints included a comparison of ORR, progression-free survival (PFS), and overall survival (OS) between patients with and without dermatologic toxicities and neuropathy. To reduce immortal time bias, Cox regression models incorporated TRAEs as time-dependent covariates to adjust for EV treatment duration as well as Eastern Cooperative Oncology Group performance status (ECOG PS), hemoglobin, and liver metastases.Between 2018 and 2023, 485 patients with aUC received > 1 dose of EV monotherapy. Most (67%) received > 2 prior therapy lines. Any grade TRAEs occurred in 77%, most frequently neuropathy (36%) and dermatologic toxicities (27%); 57% required treatment modification and 21% discontinued EV, primarily due to neuropathy (9%) and fatigue (3%). Patients with dermatologic toxicities and neuropathy had higher ORR (56% vs. 42%; p = 0.007 and 64% vs. 35%; p < 0.0001, respectively). Neuropathy was independently associated with improved OS (HR 0.66; 95% CI 0.50-0.87; p = 0.002); dermatologic TRAEs were not associated with PFS or OS benefit.RESULTSBetween 2018 and 2023, 485 patients with aUC received > 1 dose of EV monotherapy. Most (67%) received > 2 prior therapy lines. Any grade TRAEs occurred in 77%, most frequently neuropathy (36%) and dermatologic toxicities (27%); 57% required treatment modification and 21% discontinued EV, primarily due to neuropathy (9%) and fatigue (3%). Patients with dermatologic toxicities and neuropathy had higher ORR (56% vs. 42%; p = 0.007 and 64% vs. 35%; p < 0.0001, respectively). Neuropathy was independently associated with improved OS (HR 0.66; 95% CI 0.50-0.87; p = 0.002); dermatologic TRAEs were not associated with PFS or OS benefit.EV safety outside clinical trials was consistent with prior reports, with no new signals. Treatment modifications were most often due to neuropathy, dermatologic toxicities, and fatigue. Both dermatologic toxicities and neuropathy correlated with higher ORR, but only neuropathy was independently associated with improved OS.CONCLUSIONSEV safety outside clinical trials was consistent with prior reports, with no new signals. Treatment modifications were most often due to neuropathy, dermatologic toxicities, and fatigue. Both dermatologic toxicities and neuropathy correlated with higher ORR, but only neuropathy was independently associated with improved OS.
Details
- Title: Subtitle
- Treatment-Related Adverse Events and Associated Outcomes in Patients With Advanced Urothelial Carcinoma Treated With Enfortumab Vedotin: Analysis of the UNITE Study
- Creators
- Amanda Nizam - Cleveland ClinicCharles B Nguyen - University of MichiganJinju Li - University of MichiganEmily C Zabor - Cleveland Clinic Lerner College of MedicinePavlos Msaouel - The University of Texas MD Anderson Cancer CenterCindy Y Jiang - The University of Texas MD Anderson Cancer CenterOmar Alhalabi - The University of Texas MD Anderson Cancer CenterEugene Oh - University of MichiganMatthew P Davidsohn - Dana-Farber Cancer InstituteIlana B Epstein - Dana-Farber Cancer InstituteDimitra Rafailia Bakaloudi - University of WashingtonRafee Talukder - Baylor College of MedicineTanya Jindal - University of California, San FranciscoAmy K Taylor - University of Wisconsin Carbone Cancer CenterMichael J Glover - Stanford UniversityAli Raza Khaki - Stanford UniversityEmily Lemke - Medical College of WisconsinHannah Mabey - University of North Carolina at Chapel HillBashar Abuqayas - University of IowaAlbert Jang - Tulane UniversityJason R Brown - University Hospitals Seidman Cancer CenterSean T Evans - Emory UniversityCameron Pywell - University of Alabama at BirminghamArnab Basu - University of Alabama at BirminghamMehmet A Bilen - Emory UniversityPedro C Barata - Tulane UniversityYousef Zakharia - University of IowaMatthew I Milowsky - University of North Carolina at Chapel HillDeepak Kilari - Medical College of WisconsinChristopher J Hoimes - Duke Medical CenterSumit A Shah - Stanford UniversityHamid Emamekhoo - University of Wisconsin Carbone Cancer CenterNancy B Davis - Vanderbilt University Medical CenterShilpa Gupta - Cleveland ClinicPetros Grivas - University of WashingtonJoaquim Bellmunt - Dana-Farber Cancer InstituteMatthew T Campbell - The University of Texas MD Anderson Cancer CenterAjjai S Alva - University of MichiganVadim S Koshkin - University of California, San Francisco
- Resource Type
- Journal article
- Publication Details
- Cancer medicine (Malden, MA), Vol.14(19), e71284
- DOI
- 10.1002/cam4.71284
- PMID
- 41031719
- PMCID
- PMC12486332
- NLM abbreviation
- Cancer Med
- ISSN
- 2045-7634
- eISSN
- 2045-7634
- Publisher
- Wiley
- Language
- English
- Date published
- 10/01/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; General Internal Medicine; Internal Medicine
- Record Identifier
- 9984966757802771
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