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 versus 6.3 months (HR 0.87 [0.73-1.04]; P = .11), and median OS 14.4 versus 13.0 months (HR 0.88 [0.73-1.07]; P = .21), Although discontinuation rate due to intolerance was significantly higher for patients with baseline neuropathy (26% vs. 18%; P = .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 versus 6.7 months (HR 1.24 [1.01-1.52]; P = .04), and median OS 13.7 versus 13.3 months (HR 1.06 [0.84-1.34]; P = .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.
Clinical genitourinary cancer. 2026 Jan 10 [Epub ahead of print]
Albert Jang, Tanya Jindal, Ali Raza Khaki, Cindy Y Jiang, Omar Alhalabi, Charles B Nguyen, Irene Tsung, Eugene Oh, Ilana Epstein, Dimitra Rafailia Bakaloudi, Salvador Jaime-Casas, Amanda Nizam, Michael Glover, Hannah Mabey, Amy Taylor, Sean Evans, Denny Shin, Cameron Pywell, Bashar Abuqayas, Pedro C Barata, Yousef Zakharia, Arnab Basu, Deepak Kilari, Mehmet A Bilen, Hamid Emamekhoo, Matthew Milowsky, Christopher J Hoimes, Nancy Davis, Sumit Shah, Shilpa Gupta, Abishek Tripathi, Petros Grivas, Joaquim Bellmunt, Ajjai Alva, Matthew T Campbell, Zhengyi Chen, Pingfu Fu, Vadim S Koshkin, Jason R Brown
University Hospitals Seidman Cancer Center, Division of Solid Tumor Oncology, Department of Medicine, Cleveland, OH, USA; Tulane Cancer Center, Section of Hematology & Medical Oncology, Department of Medicine, New Orleans, LA, USA; Case Western Reserve University., University of California San Francisco, Helen Diller Family Cancer Center, Division of Hematology and Oncology, Department of Medicine, San Francisco, CA, USA., Stanford Cancer Institute, Division of Oncology, Department of Medicine, Palo Alto, CA, USA., University of Texas, MD Anderson Cancer Center, Department of Genitourinary Medical Oncology, Houston, TX, USA., University of Michigan Rogel Cancer Center, Division of Hematology and Oncology, Department of Internal Medicine, Ann Arbor, MI, USA., Dana-Farber Cancer Institute, Department of Medical Oncology, Boston, MA, USA., University of Washington, Fred Hutch Cancer Center, Division of Hematology and Oncology, Department of Medicine, Seattle, WA, USA; Albert Einstein College of Medicine/Jacobi Medical Center, Department of Internal Medicine, Bronx, NY, USA., City of Hope Comprehensive Cancer Center, Department of Medical Oncology & Experimental Therapeutics, Duarte, CA, USA., Case Western Reserve University; Cleveland Clinic Taussig Cancer Institute, Department of Hematology and Medical Oncology, Cleveland, OH, USA., University of North Carolina Lineberger Comprehensive Cancer Center, Division of Oncology, Department of Medicine, Chapel Hill, NC, USA., University of Wisconsin Carbone Cancer Center, Division of Hematology, Medical Oncology and Palliative Care, Department of Medicine, Madison, WI, USA., Winship Cancer Institute at Emory University, Department of Hematology and Medical Oncology, Atlanta, GA, USA., University of Alabama at Birmingham O'Neal Comprehensive Cancer Center, Division of Hematology and Oncology, Department of Medicine, Birmingham, AL, USA., University of Iowa Holden Comprehensive Cancer Center, Division of Hematology, Oncology, and Blood & Marrow Transplantation, Department of Internal Medicine, Iowa City, IA, USA., Medical College of Wisconsin Cancer Center, Division of Hematology and Oncology, Department of Medicine, Milwaukee, WI, USA., Duke Cancer Center, Division of Medical Oncology, Department of Medicine, Durham, NC, USA., Vanderbilt-Ingram Cancer Center, Division of Hematology and Oncology, Department of Medicine, Nashville, TN, USA., University of Washington, Fred Hutch Cancer Center, Division of Hematology and Oncology, Department of Medicine, Seattle, WA, USA., Case Western Reserve University., University Hospitals Seidman Cancer Center, Division of Solid Tumor Oncology, Department of Medicine, Cleveland, OH, USA; Case Western Reserve University. Electronic address: .