Effects of steroid pretreatment on adverse events and overall survival during enfortumab vedotin in urothelial carcinoma.

731 Background: Enfortumab vedotin (EV) is a standard subsequent therapy for patients with locally advanced or metastatic urothelial carcinoma (la/mUC). Although EV is effective, treatment-related adverse events (AEs), particularly the high incidence of skin toxicities, remain a major problem. Whether prophylactic steroid pretreatment can effectively reduce these toxicities is unknown. We aimed to evaluate the influence of steroid pretreatment on toxicity and survival outcomes in patients receiving EV monotherapy. Methods: We retrospectively analyzed 157 patients with la/mUC treated with EV monotherapy. Patients were stratified into those with prophylactic steroid pretreatment prior to EV initiation (pre-EV steroids, n = 20) and those without (no pre-EV steroids, n = 137). Clinical outcomes included the incidence and type of AEs, best objective response, disease-free survival (DFS), and overall survival (OS). Results: Steroid pretreatment was associated with a significantly lower incidence of skin AEs (10% vs. 62.7%, P < 0.001) and reduced number of cumulative AEs (median 1 vs. 2, P = 0.018). The incidence of grade ≥3 AEs was not significantly different between groups. Best objective response rates were comparable. However, patients with steroid pretreatment showed inferior OS compared to those without (median OS 10.3 vs. 17.4 months, P = 0.008), while DFS showed no significant difference. Multivariable analysis confirmed steroid pretreatment as an independent factor for reduced skin AEs (OR 0.08, P = 0.001) but worse OS (HR 1.99, P = 0.038). Conclusions: Steroid pretreatment during EV monotherapy mitigates skin toxicities but may compromise overall survival. Careful patient selection and judicious use of steroids are warranted to balance safety and efficacy in EV treatment for la/mUC.