Impact of Early Relative Dose Intensity on Survival in Patients Receiving Enfortumab Vedotin for Metastatic Urothelial Carcinoma: A Japanese Real-World Multicenter Study.

OBJECTIVE

This study aimed to evaluate the clinical relevance of early relative dose intensity (eRDI) during enfortumab vedotin (EV) monotherapy in patients with metastatic urothelial carcinoma (mUC) based on a Japanese real-world multicenter cohort.

METHODS

We retrospectively analyzed 119 patients with mUC who received EV. The temporal trend of total relative dose intensity (tRDI), defined as the cumulative relative dose intensity during treatment, was assessed over the first 5 months. eRDI, calculated as the mean RDI over the initial 3 months, was also evaluated. Survival analyses were performed in 84 patients evaluable beyond the first radiographic assessment, excluding those with early progressive disease (PD). Patients were stratified by eRDI (≥ 80% vs. < 80%), and progression-free survival (PFS) and overall survival (OS) were compared. Subgroup analyses were conducted according to the presence or absence of adverse event-related dose modification (AE-related DM).

RESULTS

Dose intensity gradually declined during the early treatment phase. The eRDI was not significantly associated with PFS or OS in the PD-excluded cohort (n = 84). However, among patients without AE-related DM (n = 44), high eRDI was associated with significantly longer PFS (median 11.7 vs. 4.2 months; p = 0.001) and OS (not reached vs. 13.8 months; p = 0.021). No significant association was observed between eRDI and survival in patients with AE-related DM.

CONCLUSIONS

Although eRDI was not an overall significant prognostic factor, it showed clinical relevance in patients without AE-related DM. These findings underscore the importance of preserving eRDI in patients with sufficient tolerability and support individualized dosing strategies for EV therapy.