Clinical Use of Comprehensive Genomic Profiling Tests in Intrahepatic Cholangiocarcinoma: A Single-Center Retrospective Study

Abstract

The clinical utility of comprehensive genomic profiling (CGP) in intrahepatic cholangiocarcinoma (ICC) remains to be fully elucidated. This study analysed CGP test results and evaluated treatment outcomes with fibroblast growth factor receptor (FGFR) inhibitors in patients with ICC, aiming to assess their efficacy in cases with specific FGFR alterations and to explore how CGP can inform personalised treatment strategies. We retrospectively reviewed clinical data from 52 patients with pathologically confirmed advanced ICC, who successfully underwent the CGP test at a Japanese cancer referral centre between November 2019 and March 2023. The median patient age was 67 years. CGP test identified one patient (1.9%) with a high tumour mutation burden (TMB) and revealed therapeutically relevant oncogenic driver gene alterations in 32.7% of cases. The most frequently detected alterations were FGFR2 alterations (15.4%) and isocitrate dehydrogenase 1 mutations (9.6%). Based on CGP results, nine patients—eight with FGFR2 fusions or rearrangements and one with high TMB—were eligible for approved targeted therapies. Among these, four patients treated with pemigatinib achieved stable disease, with a median treatment duration of 244 days. Notably, one patient with an FGFR2 fusion responded to pemigatinib following futibatinib failure. CGP test, when implemented in a timely manner, can serve as a valuable tool in clinical practice for identifying novel therapeutic options for patients with advanced ICC. Furthermore, sequential therapy with FGFR inhibitors may be an effective strategy for managing patients with FGFR2 fusions or rearrangements.