Enfortumab vedotin and pembrolizumab (EVP) outcomes in patients (pts) with advanced urothelial carcinoma (aUC) and FGFR3 alterations: UNITE study analysis.

668 Background: EVP is the preferred 1 st line (1L) therapy for aUC pts and is increasingly used in the perioperative setting. Data on EVP outcomes in pts with FGFR3-altered aUC are limited. Methods: We analyzed aUC pts treated with EVP who had tumor genomic profiling in the multi-site retrospective UNITE study. Pts with and without FGFR3 alterations were compared using χ 2 test and logistic regression for observed response rate (ORR) and disease control rate (DCR). Log-rank test and Cox proportional hazard models were used to assess duration of response (DOR), progression-free survival (PFS), and overall survival (OS) from EVP start. Results: 521 pts from 16 sites were treated with EVP, including 313 pts with genomic profiling data. Median age was 71, 74% were male, 84% were Caucasian, 82% had ECOG PS 0-1, 20% had liver metastases, and 73% received 1L EVP. 67 pts (21%) had FGFR3 alterations, of which 73% had point mutations, 19% had fusions, and 9% had amplifications (1 pt had both fusion and amp). FGFR3-altered pts had more upper tract primary tumor (39% vs. 24%, p = 0.02), pure urothelial histology (82% vs. 61%, p = 0.002), and non-liver visceral metastases (60% vs. 45%, p = 0.04) relative to wild type (WT). At median follow-up of 8.3 mos from EVP start, the overall cohort had ORR 53%, DCR 82%, median DOR (mDOR) 9.9 mos (95% CI 7.7-11.5 mos), median PFS (mPFS) 6.9 mos (95% CI 6.1-10.2 mos), and median OS (mOS) 18.9 mos (95% CI 14.8-33.5 mos). WT pts had ORR 53%, DCR 80%, mDOR 9.0 mos, mPFS 7.4 mos, and mOS 19.8 mos. FGFR3-altered pts had ORR 53%, DCR 90%, mDOR 10.6 mos, mPFS 6.5 mos, and mOS 13.1 mos. The presence of FGFR3 alterations was not associated with significant outcome differences with EVP as 1L or subsequent-line (2L+) therapy (Table). Pts with FGFR3 amps trended towards worse PFS. Conclusions: In this retrospective study, aUC pts with FGFR3 alterations receiving EVP had concordant treatment outcomes with WT patients. These hypothesis-generating findings require validation in larger cohorts. ORR: OR (95% CI) DCR: OR (95% CI) DOR: HR (95% CI) PFS: HR (95% CI) OS: HR (95% CI) FGFR3 altered vs. WT All EVP (n=313) 0.99 (0.6-1.8, p=0.98) 2.13 (0.9-5.9, p=0.10) 0.99 (0.7-1.5, p=0.96) 1.04 (0.7-1.5, p=0.84) 1.06 (0.7-1.6, p=0.78) 1L EVP (n=224) 0.93 (0.5-1.9, p=0.84) 1.72 (0.6-6.3, p=0.34) 0.91 (0.6-1.4, p=0.70) 1.06 (0.7-1.7. p=0.81) 1.02 (0.6-1.9, p=0.94) 2L+ EVP (n=85) 1.23 (0.4-3.7, p=0.70) 3.23 (0.8-20, p=0.14) 1.30 (0.5-3.2, p=0.57) 0.88 (0.5-1.6, p=0.70) 1.03 (0.5-2.0, p=0.92) FGFR3 alteration type vs. WT Point mut (n=49) 0.93 (0.5-1.9, p=0.85) 1.82 (0.7-5.6, p=0.24) 1.06 (0.7-1.7, p=0.80) 1.09 (0.7-1.6, p=0.70) 1.04 (0.6-1.7, p=0.87) Fusion (n=13) 0.89 (0.3-2.9, p=0.85) NA (100% DCR) 0.62 (0.3-1.4, p=0.25) 0.81 (0.4-1.7, p=0.57) 1.28 (0.6-2.8, p=0.53) Amp (n=6) 0.89 (0.1-7.7, p=0.91) 0.75 (0.1-16.7, p=0.81) 2.63 (0.6-11.1, p=0.18) 2.32 (0.9-6.3, p=0.09) 1.7 (0.5-5.3, p=0.39)