4569 Background: Enfortumab vedotin plus pembrolizumab (EV±P) is standard-of-care for patients (pts) with locally advanced/metastatic urothelial carcinoma (la/mUC), although not all pts experience durable benefit. Tumor-informed circulating tumor DNA (ctDNA) assays enable a personalized, real-time assessment of disease kinetics, and early ctDNA dynamics (24 weeks (HR: 6.8; 95% CI: 2.5–18.6; p=0.0002) was strongly associated with inferior PFS. Findings were similar for OS (12-24wk: HR: 7.2, 95% CI: 1.7-31.3; p=0.008; >24wk: HR=3.8, CI: 1.2-12.3; p=0.03). Conclusions: Longitudinal ctDNA dynamics are strongly prognostic in pts with la/mUC treated with EV±P, even when assessed beyond 12 weeks from treatment start. Sustained ctDNA negativity further identifies pts with durable clinical benefit. These findings support ctDNA as a potentially complementary biomarker to standard imaging in this clinical context.
Ayanambakkam et al. (Wed,) studied this question.