Background: Cholangiocarcinoma (CCA) is the second most common liver malignancy after hepatocellular carcinoma and is difficult to treat with high rates of metastasis. The isocitrate dehydrogenase-1 (IDH1) inhibitor ivosidenib has emerged as a promising second-line therapy for CCA patients with IDH1 mutations.
Methods: We conducted a systematic review and meta-analysis to examine ivosidenib's impact on patient survival in advanced-stage CCA patients, following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.
Results: A total of 317 patients across four studies were analysed in this review, with 256 ivosidenib-treated patients and 61 placebo-treated patients. Almost all patients have intrahepatic CCA. Ivosidenib was found to improve advanced CCA patient outcomes in median progression-free survival (PFS) (Range: 2.7-4.4 months), median overall survival (OS) (Range: 10.3–15 months), objective response rate (ORR) (Range: 2.4%–18.2%), and DCR (Range: 50.0%–63.6%), compared to outcomes in placebo-treated advanced CCA (PFS = 1.4 months, OS = 7.5 months, ORR = 0% and DCR = 27.9%). Using individual-level data and a random effects model, patient survival was calculated with a hazard ratio of 0.29 (95% confidence interval 0.21–0.42, p = 5.6 × 10-12). Common adverse events include nausea, vomiting, and abdominal pain, but QT prolongation was observed in between 5.5% and 9.1% of patients.
Conclusion: Our analysis suggests that pooled ivosidenib-treated patients with advanced CCA possess better PFS and OS compared to placebo-treated patients. However, studies combining ivosidenib with checkpoint blockade immunotherapy drugs or other targeted therapies have yet to be conducted.
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2026 The Author(s). Clinical and Translational Discovery published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.
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