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

Clin Genitourin Cancer. 2026 Mar;24(2):102501. doi: 10.1016/j.clgc.2026.102501. Epub 2026 Jan 10.

Abstract

Introduction: 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.

Patients and methods: 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.

Results: 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).

Conclusion: 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.

Keywords: Antibody-drug conjugate; Bladder cancer; Hyperglycemia; Survival; Toxicity.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Carcinoma, Transitional Cell* / drug therapy
  • Carcinoma, Transitional Cell* / mortality
  • Carcinoma, Transitional Cell* / pathology
  • Databases, Factual
  • Diabetes Mellitus* / epidemiology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Peripheral Nervous System Diseases* / epidemiology
  • Progression-Free Survival
  • Retrospective Studies
  • Treatment Outcome
  • Urologic Neoplasms* / drug therapy