Real-world genomic testing, treatment, and outcomes in patients with cholangiocarcinoma with FGFR2 fusions/rearrangements.

Abstract

e16168 Background: Several fibroblast growth factor receptor (FGFR) inhibitors have been recently approved or are in development for the treatment of cholangiocarcinoma (CCA) with FGFR2 fusions/rearrangements (f/r), such as the ATP-competitive inhibitors pemigatinib and infigratinib (FDA-approved in 2020/2021) and the covalent inhibitor futibatinib, which has shown efficacy in a pivotal phase 2 trial. To inform future evaluations of the impact of these agents in clinical practice, and understand other existing gaps in care, we investigated the characteristics and clinical management of patients with CCA and FGFR2 f/r prior to 2021. Methods: This real-world, retrospective cohort study used de-identified, patient-level electronic health records data from Cancer Treatment Centers of America (CTCA) to identify adults with a diagnosis of advanced intrahepatic CCA (iCCA) who received genomic testing between 2013-2021. Clinical/demographic characteristics, time to genomic testing, treatment patterns, and outcomes of patients with and without FGFR2 f/r were described. Results: 23 patients with FGFR2 f/r and 88 with FGFR wild-type (wt) iCCA were identified. Compared to FGFR wt, FGFR2 f/r had a higher proportion of female (65.2 vs 45.5%) and Black (39.1 vs 18.2%) patients (Table). Mean age at diagnosis was ̃60 y and >60% were diagnosed with stage 4 disease in both cohorts; 91.3% of f/r and 78.4% of wt patients had an ECOG PS 0/1. Median time from diagnosis to genomic testing was ̃5 mo; upon entry to CTCA, median time to testing was <2 mo. 17/23 patients in the f/r cohort had FGFR2 fusions (4 BICC1, 13 other). Three FGFR2 f/r patients received an FGFR inhibitor (pemigatinib) as next treatment after testing in 2020. A trend towards longer median overall survival in the f/r vs wt group (24.5 vs 17.8 mo), and a correlation of survival with ECOG PS were observed. Conclusions: This analysis provides insight into the real-world characteristics, clinical management and outcomes among patients with iCCA and FGFR2 f/r, predominantly prior to the introduction of FGFR inhibitors, providing a baseline for further study as the treatment landscape evolves. Of note, the time lag between diagnosis and genomic testing before entry to CTCA underlines the need for earlier testing to guide optimal therapy in clinical practice. [Table: see text]