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This is a video synopsis/summary of a OncLive Insights involving Lipika Goyal, MD; Chaundra Bishop; R. Katie Kelley, MD; and Caroline Kuhlman, NP.

Dr Kelley discusses findings from a recent multi-center study of intrahepatic cholangiocarcinoma in patients under age 50 showing higher rates of targetable FGFR2 fusions among young patients and women. For 29 year-old cholangiocarcinoma patient Chandra Bishop, who has far outlived typical prognosis thanks to personalized therapy, molecular profiling found an FGFR2 fusion guiding experimental treatment.

Dr Kelley notes 5-year survival is only 15% to 20% for early-stage ICC and under 5% in metastatic disease, with median survival around 1 year on chemotherapy. Genomic testing identifies targetable mutations to prolong survival with newer therapies. She advises testing all patients with advanced cholangiocarcinoma needing systemic therapy given approvals for FGFR and IDH1 inhibitors. Testing should use a panel covering FGFR2 rearrangements along with other alterations. About 40% of patients with intrahepatic cholangiocarcinoma have a targetable abnormality. Dr Kelley also suggests considering testing high-risk patients even prior to recurrence to allow faster trial access if the cancer returns.

Ideally, profiling is performed up front when starting systemic therapy given limited tissue, need for rapid trial decisions, and option of liquid biopsy if tissue is inadequate. Apart from FGFR2 fusions, HER2 amplifications, IDH1 mutations, BRAF V600E mutations, microsatellite instability, high tumor mutational burden, NTRK fusions, and RET fusions are targetable alterations. In extrahepatic disease, HER2 alterations are more common, seen in 15% to 20%.

Dr Kelley explains how fusions, rearrangements/translocations, mutations, and amplifications cause pathogenic cellular growth signaling. Fusions abnormally couple a growth-promoting gene like FGFR2 to a constantly active partner gene, causing constitutive signaling. Mutations alter the coding region to hyperactivate proteins or prevent normal checks on activity. Amplifications increase gene copy number, overproducing growth factors. These distinctions are denoted on genomic profiling reports and guide matched targeted therapy.

In summary, genomic testing to match patients with advanced cholangiocarcinoma with personalized therapies based on targetable molecular alterations has become standard of care. Testing should be obtained at systemic therapy initiation due to tissue limitations, need for rapid trial decisions, and optional liquid biopsy. Beyond FGFR2 fusions, targetable mutations in intrahepatic cholangiocarcinoma include HER2, IDH1, and BRAF, while extrahepatic disease sees more HER2 changes. Understanding different mutation categories guides appropriate targeted therapy.

*Video synopsis is AI-generated and reviewed by OncLive® editorial staff.