Impact of Initial Relative Dose Intensity on Tumor Response and Survival Outcomes in Enfortumab Vedotin Monotherapy for Previously Treated Advanced Urothelial Carcinoma: A Real-world Analysis From a Multicenter Study.

Objective: To provide real-world evidence regarding the association between the initial relative dose intensity (RDI) of enfortumab vedotin (iRDI-EV) during the first 2 to 3 cycles for locally advanced or metastatic urothelial carcinoma (la/mUC) and patient characteristics, including EV-Ineligible criTeriA (EVITA), tumor response, and survival.

Methods: A multicenter database registered 83 patients with locally advanced or metastatic treated with late-line EV monotherapy between 2021 and 2023. The iRDI-EV was calculated based on the dose modification during the first 2 to 3 cycles. A dose of 1.25 mg/kg on days 1, 8, and 15 of a 28-day cycle was considered the standard full regimen. Patients were categorized into RDI-1 (lowest), RDI-2, RDI-3, and RDI-full (100% RDI) groups.

Results: In total, 68 patients were available for iRDI-EV analysis and response evaluation. The overall median iRDI-EV was 87%, with 14, 13, 13, and 28 patients in the 4 groups exhibiting median iRDI-EV of 62%, 73%, 83%, and 100%, respectively. No clear association between the iRDI-EV and objective response was observed. The disease control rate was significantly higher in the RDI-full group (96%) than in the other groups. The patients in higher RDI groups (RDI-3/RDI-full) had longer progression-free survival than the lower RDI groups (RDI-1/RDI-2), with no difference in overall survival. A multiple linear regression analysis revealed higher iRDI-EV was a strong contributor to better response and longer survival. Of the 83 patients, 4 met ≥2 EVITA, exhibiting a higher risk of progression, whereas 79 had EVITA ≤1.

Conclusions: Oncologists must continue to learn from real-world data on late-line EV monotherapy for combination therapy.