Association of Prophylactic Intravenous Corticosteroid Premedication With Toxicity and Survival in Patients Receiving Enfortumab Vedotin for Locally Advanced or Metastatic Urothelial Carcinoma.

OBJECTIVES

Enfortumab vedotin (EV) is the standard treatment for locally advanced or metastatic urothelial carcinoma (la/mUC), though skin toxicities are problematic. We evaluated whether prophylactic corticosteroid premedication is associated with reduced toxicity and survival outcomes.

METHODS

We retrospectively analyzed 157 patients with la/mUC receiving EV monotherapy, stratified by prophylactic intravenous dexamethasone (6.6 mg) premedication (pre-EV steroid, n = 20) or not (no pre-EV steroid, n = 137). Endpoints included the incidence of EV-related adverse events (AEs), objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Inverse probability of treatment weighting (IPTW) was used to adjust for baseline imbalances.

RESULTS

Corticosteroid premedication was associated with a significantly lower incidence of skin AEs (10% vs. 62.7%, p < 0.001) and a reduced number of cumulative AEs (median 1 vs. 2, p = 0.018). The ORR were comparable. However, patients with steroid premedication showed inferior OS compared to those without (median OS 10.3 vs. 17.4 months, p = 0.008), while PFS showed no significant difference. Multivariable analysis confirmed corticosteroid premedication as an independent predictor of reduced skin AEs (OR 0.08, p = 0.001); however, it was associated with worse OS (HR 1.91, p = 0.048), with no significant impact on PFS. In the IPTW-adjusted analysis, corticosteroid premedication remained significantly associated with worse OS.

CONCLUSIONS

Corticosteroid premedication reduces skin toxicities during EV monotherapy, but its impact on survival remains uncertain and requires validation in larger studies.