Enfortumab Vedotin for Metastatic Urothelial Carcinoma: Comprehensive Treatment Outcomes and Prognostic Insights From a Multicenter Real-World Study (YUSHIMA Study)

This multicenter retrospective study evaluated the real-world efficacy and safety of enfortumab vedotin (EV) in patients with metastatic urothelial carcinoma. Despite interruptions and dose reductions, EV demonstrated comparable outcomes to the EV-301 trial with acceptable toxicity. Cutaneous adverse events were associated with longer progression-free survival and overall survival, suggesting a potential favorable prognostic impact. Introduction: Enfortumab vedotin (EV) currently plays a predominant role in the evolving treatment paradigm of metastatic urothelial carcinoma (mUC). However, large-scale real-world data on EV remain limited. This multicenter retrospective study comprehensively evaluated treatment outcomes and prognostic factors of EV monotherapy for mUC. Patients and Methods: A total of 115 consecutive patients with mUC who received EV monotherapy between 2021 and 2023 were analyzed. Baseline characteristics and treatment outcomes were collected. Progression-free survival (PFS), over-all survival (OS), best overall response, treatment-related adverse events (TRAEs), and prognostic factors associated with PFS and OS were analyzed. Results: The median age was 74 years, and 18 patients (16%) had an performance status (PS) of >= 2. During the median follow-up of 7.1 months, median PFS was 6.7 months and median OS was 12.9 months. Eighty-six patients (74%) experienced interruption or dose reduction of EV, resulting in a median relative dose intensity (RDI) of 77.4%. The objective response rate was 49%, and the disease control rate was 69%. Eighty-eight patients (77%) experienced TRAEs, including cutaneous AEs observed in 58 patients (50%). In multivariable analysis using pretreatment factors, PS >= 1, liver metastasis, and low albumin level were associated with shorter PFS and OS. With RDI and AEs incorporated in the models, the presence of cutaneous AE was independently associated with longer PFS and OS. Conclusion: This real-world study demonstrated comparable treatment efficacy and acceptable TRAEs compared to clinical trials. The presence of cutaneous AE is a potentially favorable prognostic factor for mUC patients treated with EV.