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.

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.

Duke Scholars

Author Christopher Hoimes Medicine, Medical Oncology