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The combination of gemcitabine and cisplatin remains the standard-of-care first-line therapeutic option in patients with the unresectable disease based on the encouraging phase II and phase III trials (ABC-02). Recently, the combination of durvalumab, gemcitabine, and cisplatin has shown modest but statistically significant improvement in median overall survival (OS) as compared to that of the gemcitabine–cisplatin combination. Systemic therapy options such as the combination of 5-flurouracil (5-FU) and oxaliplatin (FOLFOX), 5-FU and liposomal irinotecan, and trifluridine/tipiracil (TAS-102) and irinotecan have shown encouraging results. Therapies targeting  FGFR2  fusions/rearrangements,  BRAF  mutations, microsatellite high tumors,  HER2  amplifications, and  IDH  mutations are currently being extensively evaluated in cholangiocarcinoma with encouraging results. We briefly discuss the recent advancements in targeted therapy approaches in cholangiocarcinoma with a special focus on ivosidenib. Ivosidenib is an excellent option for  IDH1 -mutant cholangiocarcinoma that progressed on first-line chemotherapy given its excellent tolerability and median OS benefit. However, a few questions remain unanswered – sequencing of targeted therapies, benefits of combining targeted therapy with systemic chemotherapy or with other treatment modalities, such as immunotherapy and localized therapies.

An evaluation of ivosidenib for the treatment of IDH1 -mutant cholangiocarcinoma