Journal article
Real-world outcomes of patients with baseline neuropathy and/or diabetes mellitus receiving enfortumab vedotin-based regimens for advanced urothelial carcinoma in the UNITE database
Clinical genitourinary cancer, 102501
01/10/2026
DOI: 10.1016/j.clgc.2026.102501
Abstract
Enfortumab vedotin (EV)-based regimens have become standard treatments for advanced urothelial carcinoma (aUC). However, clinical trials excluded clinically significant peripheral neuropathy or uncontrolled diabetes mellitus. Therefore, we characterized real-world outcomes of patients with aUC and pre-existing peripheral neuropathy and/or diabetes mellitus receiving EV-based therapies.
In the multicenter retrospective UNITE database, patients with documented baseline neuropathy and diabetes mellitus were identified. Observed response rate (ORR) and duration of response (DOR) were compared using Fisher’s exact test. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method. Multivariable Cox models were used to adjust for confounding variables, including treatment duration.
Comparing 268 patients with baseline neuropathy to 586 patients without neuropathy, median PFS was 7.2 vs. 6.3 months (HR 0.87[0.73-1.04]; p=0.11), and median OS 14.4 vs. 13.0 months (HR 0.88[0.73-1.07]; p=0.21), Although discontinuation rate due to intolerance was significantly higher for patients with baseline neuropathy (26% vs. 18%; p=0.008), these patients did not have shorter survival. Comparing 157 patients with baseline diabetes mellitus to 697 patients without diabetes mellitus, median PFS was 5.3 vs. 6.7 months (HR 1.24[1.01-1.52]; p=0.04), and median OS 13.7 vs. 13.3 months (HR 1.06[0.84-1.34]; p=0.62).
Patients with known baseline neuropathy and/or diabetes mellitus did not have worse survival outcomes receiving EV-based regimens. Patients with baseline neuropathy who discontinued EV early due to intolerance also did not exhibit worse survival. Our findings suggest despite these relevant underlying comorbidities, patients with aUC can derive benefit from EV-containing regimens, with very close monitoring.
Enfortumab vedotin (EV) has revolutionized care for patients with advanced urothelial carcinoma, although some notable side effects include neuropathy and hyperglycemia. Clinical trials have excluded patients with moderate to severe pre-existing neuropathy and/or uncontrolled diabetes mellitus. Using a ‘real-world’ database, we showed that patients with these comorbidities could still derive benefit from EV-based therapies.
Details
- Title: Subtitle
- Real-world outcomes of patients with baseline neuropathy and/or diabetes mellitus receiving enfortumab vedotin-based regimens for advanced urothelial carcinoma in the UNITE database
- Creators
- Albert Jang - University Hospitals Seidman Cancer CenterTanya Jindal - University of California, San FranciscoAli Raza Khaki - Stanford Cancer InstituteCindy Y. Jiang - The University of Texas MD Anderson Cancer CenterOmar Alhalabi - The University of Texas MD Anderson Cancer CenterCharles B. Nguyen - U-M Rogel Cancer CenterIrene Tsung - U-M Rogel Cancer CenterEugene Oh - U-M Rogel Cancer CenterIlana Epstein - Dana-Farber Cancer InstituteDimitra Rafailia Bakaloudi - University of WashingtonSalvador Jaime-Casas - City Of Hope National Medical CenterAmanda Nizam - Case Western Reserve UniversityMichael Glover - Stanford Cancer InstituteHannah Mabey - UNC Lineberger Comprehensive Cancer CenterAmy Taylor - University of Wisconsin Carbone Cancer CenterSean Evans - Winship Cancer InstituteDenny Shin - Winship Cancer InstituteCameron Pywell - University of Alabama at BirminghamBashar Abuqayas - University of IowaPedro C. Barata - University Hospitals Seidman Cancer CenterYousef Zakharia - University of Iowa Holden Comprehensive Cancer CenterArnab Basu - University of Alabama at BirminghamDeepak Kilari - Medical College of Wisconsin Cancer CenterMehmet A. Bilen - Winship Cancer InstituteHamid Emamekhoo - University of Wisconsin Carbone Cancer CenterMatthew Milowsky - UNC Lineberger Comprehensive Cancer CenterChristopher J. Hoimes - Duke Cancer CenterNancy Davis - Vanderbilt-Ingram Cancer CenterSumit Shah - Stanford Cancer InstituteShilpa Gupta - Case Western Reserve UniversityAbishek Tripathi - City Of Hope National Medical CenterPetros Grivas - University of WashingtonJoaquim Bellmunt - Dana-Farber Cancer InstituteAjjai Alva - U-M Rogel Cancer CenterMatthew T. Campbell - The University of Texas MD Anderson Cancer CenterZhengyi Chen - Case Western Reserve UniversityPingfu Fu - Case Western Reserve UniversityVadim S. Koshkin - University of California, San FranciscoJason R. Brown - University Hospitals Seidman Cancer Center
- Resource Type
- Journal article
- Publication Details
- Clinical genitourinary cancer, 102501
- DOI
- 10.1016/j.clgc.2026.102501
- ISSN
- 1558-7673
- Publisher
- Elsevier Inc
- Language
- English
- Electronic publication date
- 01/10/2026
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; General Internal Medicine; Internal Medicine
- Record Identifier
- 9985121598602771
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