Association of EVITA with safety in advanced urothelial carcinoma: A multicenter real-world study

To evaluate whether the EV-ineligible criteria (EVITA) are associated with severe adverse events (AEs) and early treatment discontinuation in patients with locally advanced or metastatic urothelial carcinoma (la/mUC) treated with enfortumab vedotin (EV)-based therapy.

This multicenter retrospective study included 289 patients with la/mUC treated with first-line EV plus pembrolizumab (EVP; n = 132) or subsequent EV monotherapy (n = 157). EVITA was assessed at baseline and categorized as 0, 1, or ≥2. The primary endpoint was grade ≥3 AEs, and the secondary endpoint was early EV discontinuation due to AEs within 3 months (≤3 months). Associations were evaluated using Fisher's exact test and multivariable logistic regression adjusted for age, sex, body mass index (BMI), and treatment setting.

Patients receiving subsequent EV had higher EVITA scores than those treated with first-line EVP (EVITA ≥2: 17% vs. 6.8%, P = 0.01). EVITA was not associated with grade ≥3 AEs or major organ-specific toxicities, including skin AEs, peripheral neuropathy, fatigue, and gastrointestinal events. Early AE-related EV discontinuation occurred more frequently in patients with EVITA ≥2 (26%) than in those with EVITA 0 to 1 (11%-13%) (P = 0.03). However, in multivariable analyses, EVITA was not independently associated with grade ≥3 AEs or early discontinuation.

Baseline EVITA did not predict severe toxicity and showed only a modest, non-independent association with early EV discontinuation, indicating limited utility for identifying patients at high risk of clinically significant EV-related toxicity in real-world practice.