EVOLUTE: Enfortumab Vedotin in OLder patients with locally advanced/metastatic UroThElial carcinoma.

BACKGROUND: Enfortumab vedotin (EV) has been a standard-of-care treatment for advanced/metastatic urothelial carcinoma (a/mUC). However, real-world data regarding its safety and efficacy in older patients remain limited. This study evaluated EV outcomes in a real-world setting, focusing on age-related toxicity. PATIENTS AND METHODS: We conducted a multicenter, retrospective cohort study including 99 patients with a/mUC treated with EV monotherapy. Patients were classified by age (< 70 vs. ≥ 70 years). Grade ≥ 3 toxicity, treatment modifications, and survival were evaluated. Multivariable logistic regression was performed to identify risk factors for grade ≥ 3 toxicity. RESULTS: In the overall cohort, 33.3% experienced grade ≥ 3 toxicity. Multivariable analysis identified age ≥ 70 years as the only independent predictor for severe toxicity (Odds Ratio: 2.63, 95% Confidence Interval: 1.05-6.58; P = .039). Older patients had significantly higher rates of treatment discontinuation due to toxicity (34.6% vs. 4.3%; P < .001). Despite increased toxicity, patients aged ≥ 70 demonstrated numerically longer median PFS (6.3 vs. 3.1 months; P = .173) and OS (11.6 vs. 10.2 months; P = .830) compared to younger patients. Twelve patients receiving an upfront reduced dose (< 1.25 mg/kg) experienced no grade ≥ 3 toxicities while maintaining comparable survival outcomes to standard dosing. CONCLUSION: EV demonstrates comparable efficacy in older patients, but age ≥ 70 years is a significant predictor of severe toxicity, and close monitoring is warranted. Upfront dose reduction is a promising strategy to reduce severe toxicity without compromising efficacy and requires prospective evaluation in patients with a high comorbidity burden or reduced performance status.