{"entity":{"id":"intrahepatic-cholangiocarcinoma","kind":"cancer","name":"Intrahepatic cholangiocarcinoma","aka":["iCCA","Intrahepatic bile duct cancer","Peripheral cholangiocarcinoma","Mass-forming cholangiocarcinoma"],"tldr":"Intrahepatic cholangiocarcinoma starts in the small bile ducts inside the liver and usually appears as a liver mass rather than causing jaundice. It is the biliary cancer with the most drug targets: FGFR2 fusions treated with pemigatinib or futibatinib, IDH1 mutations with ivosidenib, and for everyone chemotherapy with the immunotherapy durvalumab or pembrolizumab.","summary":"Intrahepatic cholangiocarcinoma arises from the bile ducts beyond the second-order branches within the liver and presents as a mass, often found incidentally or with vague pain and weight loss, in contrast to the jaundice of extrahepatic tumours. Risk factors include cirrhosis, hepatitis B and C, primary sclerosing cholangitis, liver flukes in Thailand and neighbouring countries, and hepatolithiasis, but most cases in the West have none. Its genome differs from that of the rest of the biliary tree: FGFR2 fusions occur in about 10 to 15 percent, IDH1 mutations in about 15 percent, and BAP1 and ARID1A mutations are common, whereas KRAS and HER2 alterations are less frequent than in extrahepatic disease, so comprehensive sequencing at diagnosis is standard.\n\nResection is the only cure and is possible in a minority; hepatectomy with lymph node dissection is followed by six months of capecitabine after the BILCAP trial, whose per-protocol analysis showed longer survival. Recurrence is common. Liver transplantation for very early tumours in cirrhotic livers and after chemotherapy for locally advanced disease is under study, and for unresectable liver-confined disease radioembolisation, stereotactic radiotherapy and hepatic artery infusion chemotherapy are used in specialised centres.\n\nFor advanced disease gemcitabine with cisplatin (ABC-02, 2010) was the standard for a decade until TOPAZ-1 (2022) added durvalumab and KEYNOTE-966 (2023) added pembrolizumab, each modestly improving survival and producing a tail of long-term responders. After chemotherapy, targeted drugs matched to the tumour's mutation are given: pemigatinib (FIGHT-202, response rate 36 percent) and futibatinib (FOENIX-CCA2, response rate 42 percent) for FGFR2 fusions, and ivosidenib for IDH1 mutations, which in ClarIDHy extended progression-free survival from 1.4 to 2.7 months and gave a survival benefit once crossover was accounted for. Acquired resistance to FGFR inhibitors through gatekeeper mutations is tracked with circulating tumour DNA, and next-generation FGFR2 inhibitors such as tinengotinib are in trials.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Cholangiocarcinoma","links":[{"label":"FIGHT-202 (Lancet Oncology 2020)","url":"https://pubmed.ncbi.nlm.nih.gov/32203698/"},{"label":"ClarIDHy (Lancet Oncology 2020)","url":"https://pubmed.ncbi.nlm.nih.gov/32416072/"},{"label":"FOENIX-CCA2 (NEJM 2023)","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa2206834"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cholangiocarcinoma"}],"tags":["subtype-page"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"gastrointestinal","burden":"Bile duct cancer arising within the liver, the second commonest primary liver cancer after hepatocellular carcinoma and rising in incidence worldwide; it carries most of the targetable mutations in biliary cancer, with FGFR2 fusions in about one in eight and IDH1 mutations in about one in seven.","subtypes":["Mass-forming intrahepatic cholangiocarcinoma (most)","Intrahepatic cholangiocarcinoma with FGFR2 fusion (pemigatinib, futibatinib)","Intrahepatic cholangiocarcinoma with IDH1 mutation (ivosidenib)","Small-duct versus large-duct type","Fluke-associated intrahepatic cholangiocarcinoma","Combined hepatocellular-cholangiocarcinoma"],"biomarkers":["FGFR2 fusions and rearrangements (RNA or DNA sequencing)","IDH1 mutation","BAP1, ARID1A and PBRM1 (small-duct type)","HER2, BRAF V600E, NRG1 and microsatellite instability (less common)","CA 19-9 for monitoring","Circulating tumour DNA for resistance mutations under FGFR inhibition"],"standardOfCare":[{"setting":"Diagnosis","approach":"Contrast MRI and CT, biopsy, and comprehensive genomic profiling including RNA-based fusion detection for every patient.","refs":["mri","ct","cgp","ngs","fgfr2-fusion"]},{"setting":"Resectable","approach":"Hepatectomy with lymph node dissection followed by six months of adjuvant capecitabine (BILCAP).","refs":["hepatectomy","lymphadenectomy","bilcap","capecitabine"]},{"setting":"Unresectable, liver-confined","approach":"Radioembolisation, stereotactic radiotherapy or hepatic artery infusion in specialised centres, usually with systemic therapy; liver transplantation in trials.","refs":["radioembolisation-tare","sbrt","liver-transplant-oncology"]},{"setting":"Advanced, first line","approach":"Gemcitabine and cisplatin with durvalumab (TOPAZ-1) or pembrolizumab (KEYNOTE-966).","refs":["topaz-1","keynote-966","abc-02","gemcitabine-cisplatin","durvalumab","pembrolizumab","gemcis-plus-io-btc"]},{"setting":"Advanced, FGFR2 fusion after chemotherapy","approach":"Pemigatinib (FIGHT-202) or futibatinib (FOENIX-CCA2); management of hyperphosphataemia and eye toxicity.","refs":["pemigatinib","futibatinib","fight-202","foenix-cca2","fgfr2","fgfr2-fusion"]},{"setting":"Advanced, IDH1 mutation after chemotherapy","approach":"Ivosidenib (ClarIDHy).","refs":["ivosidenib","claridhy","idh"]},{"setting":"Second line without a target","approach":"FOLFOX (ABC-06); trials.","refs":["folfox","cytotoxic-chemotherapy"]}],"stateOfArt":["Intrahepatic cholangiocarcinoma was the first gastrointestinal cancer with an approved FGFR inhibitor and the first solid tumour with an approved IDH1 inhibitor.","Immunotherapy added to gemcitabine-cisplatin is now first-line standard across biliary cancers.","Tracking resistance with circulating tumour DNA and switching FGFR inhibitors is becoming routine in specialist centres."],"history":[{"year":2010,"title":"ABC-02: gemcitabine plus cisplatin becomes the standard for advanced biliary cancer","refs":["abc-02","gemcitabine-cisplatin"]},{"year":2019,"title":"BILCAP: adjuvant capecitabine after resection","refs":["bilcap","capecitabine"]},{"year":2020,"title":"FIGHT-202: pemigatinib approved for FGFR2 fusion-positive cholangiocarcinoma","refs":["fight-202","pemigatinib"]},{"year":2021,"title":"ClarIDHy: ivosidenib approved for IDH1-mutant cholangiocarcinoma","refs":["claridhy","ivosidenib"]},{"year":2022,"title":"FOENIX-CCA2: futibatinib approved; TOPAZ-1: durvalumab added to chemotherapy","refs":["foenix-cca2","futibatinib","topaz-1","durvalumab"]},{"year":2023,"title":"KEYNOTE-966: pembrolizumab added to chemotherapy","refs":["keynote-966","pembrolizumab"]}],"pipeline":["tinengotinib","first-308","idea-btc-ctdna-fgfr-resistance","liquid-biopsy","liver-transplant-oncology","radioembolisation-tare","zanidatamab"],"openProblems":["Most patients present unresectable, and recurrence after resection is common.","FGFR inhibitor resistance develops within a year through kinase domain mutations.","Rising incidence in Western countries without a clear cause."],"parent":"cholangiocarcinoma"},"route":"/cancers/intrahepatic-cholangiocarcinoma/","neighbours":{"trial":[{"id":"abc-02","kind":"trial","name":"ABC-02","route":"/trials/abc-02/"},{"id":"bilcap","kind":"trial","name":"BILCAP","route":"/trials/bilcap/"},{"id":"claridhy","kind":"trial","name":"ClarIDHy","route":"/trials/claridhy/"},{"id":"fight-202","kind":"trial","name":"FIGHT-202","route":"/trials/fight-202/"},{"id":"first-308","kind":"trial","name":"FIRST-308","route":"/trials/first-308/"},{"id":"foenix-cca2","kind":"trial","name":"FOENIX-CCA2","route":"/trials/foenix-cca2/"},{"id":"keynote-966","kind":"trial","name":"KEYNOTE-966","route":"/trials/keynote-966/"},{"id":"topaz-1","kind":"trial","name":"TOPAZ-1","route":"/trials/topaz-1/"}],"drug":[{"id":"capecitabine","kind":"drug","name":"Capecitabine","route":"/drugs/capecitabine/"},{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"},{"id":"folfox","kind":"drug","name":"FOLFOX (5-FU, leucovorin, oxaliplatin)","route":"/drugs/folfox/"},{"id":"futibatinib","kind":"drug","name":"Futibatinib","route":"/drugs/futibatinib/"},{"id":"gemcitabine-cisplatin","kind":"drug","name":"Gemcitabine + cisplatin","route":"/drugs/gemcitabine-cisplatin/"},{"id":"ivosidenib","kind":"drug","name":"Ivosidenib","route":"/drugs/ivosidenib/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"pemigatinib","kind":"drug","name":"Pemigatinib","route":"/drugs/pemigatinib/"},{"id":"tinengotinib","kind":"drug","name":"Tinengotinib","route":"/drugs/tinengotinib/"},{"id":"zanidatamab","kind":"drug","name":"Zanidatamab","route":"/drugs/zanidatamab/"}],"idea":[{"id":"idea-btc-ctdna-fgfr-resistance","kind":"idea","name":"ctDNA-guided switching among FGFR inhibitors","route":"/ideas/idea-btc-ctdna-fgfr-resistance/"}],"technology":[{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"},{"id":"ct","kind":"technology","name":"CT (computed tomography)","route":"/technologies/ct/"},{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"liver-transplant-oncology","kind":"technology","name":"Liver transplantation for cancer (Milan criteria and beyond)","route":"/technologies/liver-transplant-oncology/"},{"id":"mri","kind":"technology","name":"MRI","route":"/technologies/mri/"},{"id":"radioembolisation-tare","kind":"technology","name":"Radioembolisation (TARE / SIRT, yttrium-90)","route":"/technologies/radioembolisation-tare/"},{"id":"sbrt","kind":"technology","name":"SBRT / SABR (stereotactic radiotherapy)","route":"/technologies/sbrt/"}],"term":[{"id":"fgfr2-fusion","kind":"term","name":"FGFR2 fusions and rearrangements","route":"/terms/fgfr2-fusion/"},{"id":"hepatectomy","kind":"term","name":"Hepatectomy (liver resection)","route":"/terms/hepatectomy/"},{"id":"lymphadenectomy","kind":"term","name":"Lymphadenectomy (lymph node dissection)","route":"/terms/lymphadenectomy/"},{"id":"ngs","kind":"term","name":"Next-generation sequencing (NGS)","route":"/terms/ngs/"}],"pairing":[{"id":"gemcis-plus-io-btc","kind":"pairing","name":"Gemcitabine-cisplatin + PD-(L)1 blockade in biliary cancer","route":"/pairings/gemcis-plus-io-btc/"}],"target":[{"id":"fgfr2","kind":"target","name":"FGFR2","route":"/targets/fgfr2/"},{"id":"idh","kind":"target","name":"IDH1 / IDH2","route":"/targets/idh/"}],"cancer":[{"id":"cholangiocarcinoma","kind":"cancer","name":"Biliary tract cancer (cholangiocarcinoma)","route":"/cancers/cholangiocarcinoma/"}]}}