Elderly patients with metastatic urothelial carcinoma (mUC) often face limited treatment options due to concerns over treatment-related toxicities and frailty. The EV-301 trial's subgroup analysis indicated no significant survival benefit of enfortumab vedotin (EV) over chemotherapy in patients aged ≥75 years (HR 0.91, 95% CI: 0.55-1.51), highlighting the need for real-world data. To assess the efficacy, safety, and prognosis of EV monotherapy in patients aged ≥75 years compared to younger counterparts.

• Design: Retrospective, single-center analysis of mUC patients treated with EV between Dec 2021 and Nov 2024. • Patients: 51 cases (≥75 years: 18, <75 years: 33). Median age: 73 years (range 41-84). • Treatment History: All patients had progressed after platinum-based chemotherapy and immune checkpoint inhibitors. • Endpoints: • - Efficacy: Progression-Free Survival (PFS), Overall Survival (OS) • - Safety: Incidence and severity of adverse events (AEs) per CTCAE v5.0

• Response: -ORR: 48.5% in <75 group vs. 55.6% in ≥75 group (P=0.65). DCR: 78.8% in <75 group vs. 77.8% in ≥75 group (P > 0.99). -Duration of Response (DoR): Median 4.7 months in <75 group (95% CI: 3.0–15.6). Median 4.9 months in ≥75 group (95% CI: 1.6–9.7). • PFS: Median 5.0 months in ≥75 group vs. 5.7 months in <75 group (P=0.67). • OS(Figure1): Median 13.7 months in ≥75 group vs. 11.4 months in <75 group (P=0.537). • Adverse Events: • - Comparable incidence between age groups (Figure 2). • - Treatment discontinuation due to AEs: 0% in C5 group vs. 6.1% in <75 group. • Prognostic Analysis: Age ≥75 was not a predictor of poor OS (HR 1.31, 95% CI 0.69-2.51, P=0.411), whereas high Bellmunt risk score (≥2) was a significant predictor (HR 2.71, 95% CI 1.40-5.23, P=0.003).

EV monotherapy demonstrates comparable efficacy, safety, and prognosis in patients aged ≥75 years to those aged <75 years. Advanced age alone should not preclude the use of EV therapy in metastatic urothelial carcinoma.