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

ABSTRACT

Introduction

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.

Areas covered

We briefly discuss the recent advancements in targeted therapy approaches in cholangiocarcinoma with a special focus on ivosidenib.

Expert opinion

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.

KEYWORDS:

• Ivosidenib
• cholangiocarcinoma
• gemcitabine
• cisplatin
• precision medicine

Drug summary box

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Declaration of interest

A Mahipal serves on the advisory board for Taiho Oncology, AstraZeneca, and QED Therapeutics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has disclosed receipt of research funding and personal fees from Servier. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Authors’ contributions

S H Tella and A Mahipal wrote, edited, and approved the final version of the manuscript.

Additional information

Funding

This paper was not funded.