Real-World Toxicity and Efficacy Profile of Enfortumab Vedotin With or Without Pembrolizumab in Ultra-Elderly Patients With Advanced Urothelial Carcinoma.

PURPOSE: Enfortumab vedotin (EV) is indicated for treatment of locally advanced or metastatic urothelial carcinoma (la/mUC) as monotherapy and in combination with pembrolizumab (P). The ultra-elderly population, defined as patients aged at least 80 years, represents the minority of patients treated in prospective clinical trials with EV. This study examined the real-world toxicity profile, efficacy outcomes, and dosing strategies of EV-based therapies in ultra-elderly patients with la/mUC. MATERIALS AND METHODS: This is a retrospective analysis of 29 patients with la/mUC, aged at least 80 years, who were initiated on EV or EV plus P. The primary study endpoint was incidence and severity of EV treatment-related adverse events (TRAEs). Selected secondary endpoints included incidence of up-front dose reduction of EV and associated TRAEs, objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), and median overall survival (mOS). RESULTS: At least one EV-related TRAE was observed in 79.3% of patients, but no grade 4 or 5 toxicities were observed. Starting EV dose was 1.25 mg/kg in 20.7% of patients, 1.0 mg/kg in 48.3% of patients, 0.75 mg/kg in 17.2% of patients, and 0.5 mg/kg in 13.8% of patients, which was administered on days 1 and 8 out of a 21-day cycle. The ORR was 57.7% and the DCR was 88.5%. The mPFS and mOS were 7.82 and 11.6 months, respectively. This study is limited by its retrospective nature and limited sample size. CONCLUSION: This study did not identify excessive or unexpected toxicity from EV-based regimens in the ultra-elderly population. TRAEs were less severe at lower starting doses of EV. The efficacy of EV-based therapies appears comparable with previously published prospective data, despite up-front EV dose reduction.