Cholangiocarcinoma (CCA) comprises intrahepatic (iCCA), perihilar CCA, or distal CCA, and is often diagnosed at an advanced or metastatic stage. Mutations in the isocitrate dehydrogenase 1 (IDH1) gene are present in approximately 10% to 15% of patients with iCCA, driving tumor growth through the production of oncometabolite 2-hydroxyglutarate (2-HG). However, real-world data on clinical outcomes and treatment patterns in this molecularly defined population remain limited. This retrospective analysis, recently presented at ASCO GI 2026, characterized the management of patients with IDH1-mutant metastatic CCA.
The study used Citizen Health data from 3000 US healthcare institutions to characterize clinical features, molecular testing patterns, treatments, and outcomes among patients with IDH1-mutant CCA. Patients were followed from initial pathologic diagnosis until death or censorship at their last recorded activity. Time-to-event endpoints were also estimated using Kaplan–Meier methods.
A total of 602 patients diagnosed with CCA between 2007 and 2025 were included. The median age at diagnosis was 59.5 years (range, 22.3-85.8), and 60% of patients were female. Most patients had iCCA (61%), and 60% had advanced or metastatic disease. Biomarker testing was performed in 499 patients, and of these, 88 patients (18%) had IDH1-mutated CCA. Thirteen percent of patients had an FGFR2 rearrangement. Most commonly, tissue-based (79%) biomarker testing approaches were used. Next-generation sequencing testing methods, whether for DNA or RNA, were used in 55% of patients and immunohistochemistry in 39%.
Eighty patients (91%) received first-line (1L) systemic therapy, with gemcitabine and cisplatin (GemCis) being the most common regimen (33%). Other 1L therapies included GemCis-durvalumab (26%) and GemCis–nab-paclitaxel (15%). Median progression-free survival (PFS) in the 1L setting was 8 months, and median overall survival (OS) was 30 months, with a disease control rate (DCR) of 84%.
Second-line (2L) therapy was administered to 63 patients (72%), with ivosidenib being the most common regimen, either as monotherapy (35%) or in combination (11%). Among patients receiving ivosidenib-containing regimens, the median PFS was 6.1 months, the median OS was 25.1 months, and the DCR was 69%. In comparison, patients who received other 2L regimens had a median PFS of 4.1 months, a median OS of 20.1 months, and a DCR of 56%.
This real-world analysis highlights the role of biomarker testing in CCA and characterizes treatment patterns among patients with IDH1-mutant disease, including frequent use of GemCis-based regimens in 1L therapy and ivosidenib in 2L therapy. The observed outcomes align with results from the ClarIDHy trial and may support the use of ivosidenib as a potential 2L treatment option for patients with IDH1-mutant CCA.
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