683 Background: Enfortumab vedotin (EV) is a standard therapy for metastatic urothelial carcinoma (mUC) after platinum-based chemotherapy and immune checkpoint inhibitors. However, optimal early dosing strategies remain unclear in real-world practice. Maintaining relative dose intensity (RDI) may influence efficacy, yet the prognostic role of early RDI (eRDI) and its relationship with adverse event–related dose modification (AE-DM) are not well defined. Clarifying whether early dose modification affects outcomes is crucial for balancing efficacy and tolerability in EV therapy. Methods: We retrospectively analyzed 119 patients with mUC treated with EV monotherapy at multiple Japanese institutions from 2021 to 2024. Among them, 84 patients who underwent at least one post-baseline radiographic assessment and did not show early progressive disease (PD) were included in the efficacy analysis. Early RDI was defined as the mean RDI during the first three months. AE-DM was defined as any reduction, delay, or interruption due to toxicity. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan–Meier method and compared using the log-rank test, stratified by AE-DM status (positive or negative). Results: In the PD-excluded cohort, patients with eRDI ≥80% had significantly longer PFS and OS than those with eRDI <80% (median PFS: 8.5 vs 4.3 months, p=0.008; OS: not reached vs 11.2 months, p=0.012). Among AE-DM–negative patients, low eRDI predicted worse outcomes (median PFS: 11.7 vs 4.2 months, p=0.001; OS: not reached vs 13.8 months, p=0.021). Conversely, in AE-DM–positive patients, survival did not differ between eRDI groups, suggesting that clinically guided dose modification did not compromise efficacy. Conclusions: Early RDI predicted survival in patients who tolerated standard dosing without AE-DM, whereas dose modification for toxicity preserved efficacy. Maintaining early intensity is important for fit patients, while individualized dose modification may ensure safety and effectiveness in those with AE-DM. eRDI may serve as a practical early indicator in real-world EV therapy. Survival outcomes according to eRDI and AE-DM status. Cohort n Median PFS (months, eRDI ≥80% vs <80%) p-value Median OS (months, eRDI ≥80% vs <80%) p-value All PD-excluded 84 8.5 vs 4.3 0.008 NR vs 11.2 0.012 AE-DM (−) 49 11.7 vs 4.2 0.001 NR vs 13.8 0.021 AE-DM (+) 35 6.3 vs 6.1 0.67 15.1 vs 14.9 0.82 PFS, progression-free survival; OS, overall survival; eRDI, early relative dose intensity; PD, progressive disease; AE-DM, adverse event-related dose modification; NR, not reached.
Endo et al. (Sun,) studied this question.