Retrospective analysis of treatment responses to enfortumab vedotin combined with pembrolizumab (EVP) based on FGFR2/3 alterations in patients (pts) with advanced urothelial carcinoma (aUC).

688 Background: Reports vary as to the relationship between FGFR2/3 mutations (FGFR2/3m) and responses to EV in pts with aUC. As EVP has been rapidly adopted as first-line treatment based on results from the EV-302 trial, responses to treatment with EVP in patients with and without FGFR2/3m have not been well-described to date. We sought to examine a retrospective cohort of pts with aUC treated with EVP to determine whether there are differences in responses based on FGFR2/3m. Methods: Data from 5 academic institutions were collected from patients with aUC treated with first-line EVP from 8/13/2018 to 8/20/2025. Pts needed to have at least 1 whole body scan to assess for treatment response, which was interpreted using RECIST by the treating physician. Extracted data from the electronic health record (EHR) included demographic, clinical, and genomic variables. We also collected data on FGFR2/3m present, absent, or unknown. Those with unknown FGFR2/3 status were excluded from analysis. Primary endpoint was median PFS (mPFS), defined as time from EVP initiation to progressive disease by RECIST v1.1 criteria. Data were analyzed using descriptive statistics and Kaplan-Meier estimation. Results: Data were collected from 143 pts, with 122 pts having known FGFR2/3 status. Select clinical characteristics in the study population are outlined in Table 1. FGFR2/3m were noted in 34 pts, while 88 were wildtype (wt). Pts with FGFR2/3m experienced a shorter mPFS (5.2 months, 95% CI 4.0-24) than those with FGFR2/3 wt (16 months, 95% CI 9.2-35; p=0.029). Overall survival was not significantly different. Conclusions: While a limited retrospective dataset, shorter mPFS was observed in pts with FGFR2/3m aUC. This may inform future research development of first-line treatment of aUC in pts with FGFR2/3m. Clinical characteristics and efficacy. FGFR2/3m(n=34) FGFR2/3 wt(n=88) Age (median, range) 66 (37, 86) 73 (27, 95) Male (n,%) 24 (71%) 63 (72%) Upper Tract Primary (n,%) 11 (33%) 21 (24%) Lymph node only metastases (n,%) 24 (71%) 59 (67%) Median PFS (months, 95% CI) 5.2 (4.0, 24) 15 (9.2, 35) Median OS (months, 95% CI) 33 (24, --) 29 (20, --)