Real-world prognostic assessment of the HERO score in metastatic urothelial carcinoma treated with enfortumab vedotin (ARON-2EV study)

Abstract

Enfortumab vedotin (EV) is a standard treatment for metastatic urothelial carcinoma (mUC) after platinum-based chemotherapy and immune checkpoint inhibitors. However, reliable and clinically accessible prognostic tools for patients treated with EV remain limited. We evaluated the clinical prognostic performance of the HERO score in a large real-world cohort of EV-treated patients. Patients and methods ARON-2EV is a retrospective multicenter cohort study including patients with mUC treated with EV after platinum-based chemotherapy and immune checkpoint inhibitors. The association between the HERO score, based on hemoglobin level and neutrophil-to-lymphocyte ratio, and survival outcomes (overall survival and progression-free survival) was assessed. Response analyses were considered exploratory. Results A total of 548 patients with mUC treated with EV were included in the analysis. Median overall survival was 12.4 months and median progression-free survival was 6.8 months. The HERO score was associated with survival and response outcomes, with patients with a score of 2 experiencing the most favorable outcomes. These associations remained consistent across multivariable analyses. Conclusions In this large international real-world cohort, the HERO score was associated with survival and response outcomes in patients with mUC treated with EV, particularly through identification of a subgroup with a more favorable prognosis (score 2). However, discrimination between lower score categories was less pronounced. Further prospective refinement and evaluation of the HERO score are warranted, particularly in contemporary EV-based treatment strategies.