Enfortumab vedotin demonstrates consistent efficacy in platinum- and ICI-refractory metastatic urothelial carcinoma patients irrespective of prior response: a multicenter real-world study.

Introduction: Enfortumab vedotin (EV) is an antibody-drug conjugate (ADC) targeting nectin-4 and is widely used for patients with locally advanced or metastatic urothelial carcinoma (mUC) after prior systemic therapies. However, it remains unclear whether EV efficacy is influenced by responses to preceding platinum-based chemotherapy (PBC) or immune checkpoint inhibitors (ICI). This study evaluated the relationship between responses to prior therapy and EV outcomes in a real-world cohort. Material and methods: We retrospectively analyzed 60 patients with mUC who received EV between December 2021 and March 2024. All patients had previously undergone PBC and ICI. Based on responses to these therapies, patients were classified as responders (complete or partial response) or non-responders (stable or progressive disease). Primary endpoints were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Multivariable Cox proportional hazards models were used to evaluate factors associated with survival outcomes. Results: The overall EV ORR was 41.7%. EV responders demonstrated significantly longer PFS and OS than non-responders. No significant differences in EV efficacy were observed between responders and non-responders to prior chemotherapy or ICI. Multivariable analyses confirmed that prior treatment response was not independently associated with PFS or OS. Conclusions: EV response was strongly associated with prolonged survival. Importantly, consistent antitumor activity was observed regardless of prior treatment efficacy, suggesting that even patients refractory to PBC or ICI may derive meaningful benefit. EV should be offered promptly even for patients with double-refractory mUC, as the presence of a prior non-response does not signify compromised efficacy.