Impact of relative dose intensity on efficacy of enfortumab vedotin monotherapy in platinum and ICI resistant metastatic urothelial carcinoma: A multi-institutional real-world analysis.

Abstract

728 Background: The treatment paradigm for metastatic or locally advanced urothelial carcinoma (mUC) has shifted towards combination therapies with Enfortumab Vedotin (EV) and Pembrolizumab. Understanding EV's characteristics is crucial for optimizing treatment. The EV-101 trial showed a correlation between exposure and efficacy, but few real-world studies explore how relative dose intensity (RDI) impacts outcomes. This study examines RDI's effect on efficacy using real-world data. Methods: We retrospectively analyzed 123 mUC patients treated with EV monotherapy as third-line or later, following progression after platinum-based chemotherapy and resistance to immune checkpoint inhibitors (ICIs). Data were collected from five institutions. We evaluated overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Patients were grouped into full dose on-schedule (FDO) and dose/schedule adjusted (DSA) based on EV dose and timing until best response (BR). On DSA group, relative dose intensity (RDI) until BR (BRRDI) was measured, and patients were classified into High (BRRDI > 80), Intermediate (80 ≥ BRRDI > 70), and Low (BRRDI ≤ 70) groups for comparison. Results: Among the 123 patients, median OS (mOS) was 14.8 Ms, median PFS (mPFS) was 7.1 Ms, and ORR was 48%, with a complete response (CR) rate of 9%. In the FDO group (31 patients), mOS was 9.3 Ms, mPFS was 4.5 Ms, and ORR was 29% (CR: 0%). In the DSA group (93 patients), mOS was 17.1 Ms (p=0.002), mPFS was 8.8 Ms (p=0.019), and ORR was 56% (CR: 12.1%) (p=0.0029 for ORR, p=0.017 for CR). In the BRRDI analysis, median time to BR was 2.6 Ms. ORR for High, Intermediate, and Low groups were 50% (CR: 20%), 58% (CR: 3.4%), and 63% (CR: 9.4%), respectively, with significant differences in CR (p=0.026). Conclusions: Patients requiring dose or schedule adjustments before best response showed better ORR, OS, and PFS than those on full dose. Higher BRRDI correlated with better CR, emphasizing the need to manage adverse events while maintaining dose intensity until BR.