Clinical Outcomes of Metastatic Urothelial Carcinoma Patients Discontinuing Enfortumab Vedotin Due to Toxicity and/or Clinical Response.

INTRODUCTION: Enfortumab vedotin (EV), alone or in combination with pembrolizumab (EV/P) are established treatment for metastatic urothelial carcinoma (mUC). Patients who discontinue EV after achieving a complete or partial response (CR/PR), or due to toxicity, may maintain durable disease control. PATIENTS AND METHODS: We retrospectively analyzed 147 patients with mUC treated with ≥2 cycles of EV or EV/P at our institution. The primary endpoint was treatment-free interval (TFI) among patients who discontinued EV for ≥8 consecutive weeks due to CR/PR and/or toxicity. Patients receiving EV/P may have continued pembrolizumab after discontinuing EV. TFI was evaluated through competing risks analysis with treatment re-initiation and death modeled as competing risks by both cumulative incidence functions and Fine-Gray regression. RESULTS: A total of 73 patients discontinued EV due to toxicity and/or CR/PR. At 1 year following EV discontinuation, 41.9% of EV-treated and 68.9% of EV/P-treated patients remained alive and treatment-free. Duration of EV was not associated with TFI (EV: HR 1.02, P = .78; EV/P: HR 0.88, P = .18). Achieving CR was associated with longer TFI compared with PR (HR 2.94, P = .03). Among the 23 patients who restarted EV at progression, 21.7% achieved PR, 30.4% stable disease, and 47.8% experienced progressive disease. CONCLUSIONS: Among selected patients with mUC who discontinued EV due to toxicity or clinical response, prolonged intervals without subsequent systemic therapy were observed. EV rechallenge at progression demonstrated clinical activity in a subset of patients. Prospective studies are warranted to optimize treatment duration and explore the role of EV rechallenge.