Outcomes of Enfortumab Vedotin Treatment in Patients Ineligible for the EV-301 Trial

The EV-301 trial demonstrated the efficacy of enfortumab vedotin (EV) as a third-line treatment for metastatic urothelial carcinoma (mUC), showing significant improvement in overall survival (OS) and progression-free survival (PFS) compared to chemotherapy in patients previously treated with platinum-based therapy and immune checkpoint inhibitors. In real-world clinical practice, patients undergoing third-line treatment often have poor baseline health status, leading to the off-label use of EV in populations ineligible for clinical trials. This study aimed to evaluate the treatment outcomes of EV in both EV-301 trial-eligible and -ineligible patients.

Fifty-eight patients with mUC treated with EV across five Institutions were retrospectively evaluated and stratified based on the EV-301 trial eligibility criteria. Patients with an Eastern Cooperative Oncology Group performance status of ≥2, baseline hemoglobin level of <9 g/dl, creatinine clearance <30 ml/min, or other protocol-defined criteria were analyzed. Treatment outcomes were assessed for both groups.

Of the 58 patients, 33 (56.9%) met the EV-301 trial eligibility criteria. No significant differences were observed in PFS (median: 9.2 vs. 7.1 months, for eligible vs. ineligible patients) and OS (15.4 vs. 8.9 months). Although the objective response rate was higher in the eligible group (54.6% vs. 28.0%), there was no significant difference in the disease control rate (78.8% vs. 80.0%). Adverse events (AEs) of any grade were more frequent in the eligible group (93.9% vs. 64.0%), but the incidence of grade ≥3 AEs did not differ significantly (12.1% vs. 8.0%).

The findings of this multi-institutional study highlight the feasibility of EV treatment in EV-301 trial-ineligible patients with mUC, supporting its potential applicability in both trial-eligible and -ineligible groups.