Ivosidenib for the treatment of isocitrate dehydrogenase-1 mutant cholangiocarcinoma

ABSTRACT

Introduction: Cholangiocarcinomas (CCAs) are associated with poor survival outcomes, with limited treatment options in the unresectable or metastatic setting. A precision medicine approach to cancer treatment has revealed new therapeutic options that provide an alternative to traditional chemotherapeutic strategies. Isocitrate dehydrogenase 1 (IDH1) mutations are identified in approximately 10–15% of CCAs and may be targeted by ivosidenib, an oral selective inhibitor of mutant IDH1.

Areas covered: This review will discuss the pathogenesis of IDH1 mutant CCA and the role of ivosidenib in patients with IDH1 mutant CCA. Topics to be covered include the pharmacology, safety and clinical efficacy of ivosidenib in this patient population.

Expert opinion: Ivosidenib represents a promising treatment option for patients with IDH1 mutant CCA with a favorable side effect profile. Future studies will guide whether this targeted agent may be utilized in combination with other anticancer treatments to improve upon survival outcomes in advanced CCA.

KEYWORDS:

• Cholangiocarcinoma
• isocitrate dehydrogenase
• ivosidenib
• precision medicine

Article highlights

• Isocitrate dehydrogenase 1 (IDH1) mutations are demonstrated in approximately 10–15% of patients with advanced cholangiocarcinoma (CCA), more commonly in intrahepatic CCA.

• Ivosidenib is an oral selective inhibitor of mutant IDH1 which is approved for use in IDH1 mutant acute myeloid leukaemia.

• A large phase 3 study has demonstrated the activity of ivosidenib in patients with previously treated IDH1 mutant CCA with a 6 month and 12 month progression free survival of 32% and 22%, respectively, compared to 0% in the placebo arm.

• Ivosidenib demonstrates a favourable side effect profile compared to traditional chemotherapeutic drugs.

Declaration of interest

M Lowery has sat on the Advisory Board for Agios Pharmaceuticals for the past 3 years. 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

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.