Association of body mass index and tumor response in metastatic urothelial carcinoma treated with enfortumab vedotin: data from the ULTRA-Japan consortium

Background: Enfortumab vedotin (EV), an antibody–drug conjugate (ADC) targeting Nectin-4, has been available as standard care for metastatic urothelial carcinoma (mUC) patients who have progressed after platinum-based chemotherapy and checkpoint inhibitors (CPIs). However, the association between body mass index (BMI) and clinical outcomes for EV remains unknown. Methods: We analyzed the records of 123 mUC patients who received EV. The cohort was divided into low BMI (< 22, n = 65) and high BMI (≥ 22, n = 58) groups. Propensity score matching was performed to reduce clinical bias between the two groups. Results: In the total cohort (n = 123), the objective response rate (ORR) and disease control rate (DCR) were 46% and 68%, respectively. The ORR was significantly higher in the higher BMI group (62%, n = 58) compared to the lower BMI group (32%, n = 65). Among the pair-matched cohort (n = 100), despite reducing potential bias, the ORR remained significantly higher in the higher BMI group than in the lower BMI group (64% vs. 32%, p = 0.002). Both overall survival (OS) and radiographic progression-free survival (r-PFS) were longer in the higher BMI group compared to the lower BMI group (median OS: not reached vs. 8 months, p = 0.035; median r-PFS: 10 vs. 4 months, p < 0.001). On multivariate analyses, a higher BMI (≥ 22) was an independent predictor for achieving objective response and favorable OS in mUC patients treated with EV. Conclusions: The findings of this study suggest a potential association between high BMI and improved tumor response to EV in mUC patients with disease progression after platinum-based chemotherapy and CPIs.