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.