Multicenter retrospective cohort study of initial enfortumab vedotin dose reduction and outcomes in pretreated advanced urothelial carcinoma

Initial enfortumab vedotin (EV) dose selection is increasingly relevant in advanced urothelial carcinoma (aUC). Reduced starting doses may be selected for some patients, but their associations with clinical outomes and tolerability remain uncertain. A multicenter retrospective cohort study in South Korea evaluated the association of physician-selected initial EV monotherapy dose reduction with clinical outcomes among aUC patients previously treated with platinum-based chemotherapy and immune checkpoint inhibition. The primary comparison was reduced-dose (≥ 10% dose reduction) versus full-dose (< 10% reduction). Among 368 patients, initial dose reduction of 10% or greater was not significantly associated with progression-free survival or overall survival. Objective response occurred in 44.5% of response-evaluable patients in the reduced-dose group and 53.1% of patients in the full-dose group. Post hoc analyses found a lower incidence of grade 3 or higher peripheral neuropathy and a shorter progression-free survival with reductions exceeding 20% versus full dose. The authors conclude that these findings do not establish equivalence or warrant routine initial dose reduction and require prospective evaluation of initial EV dosing.