Ivosidenib in IDH-mutant cholangiocarcinoma: where do we stand?

ABSTRACT

Introduction: Cholangiocarcinomas (CCAs) are rare and heterogeneous malignancies associated with poor prognosis, with most of the patients presenting with advanced disease at diagnosis. The recent advent of molecular profiling has led to the identification of several druggable genetic aberrations, and among these, there is an increasing interest in isocitrate dehydrogenase-1 (IDH-1) mutations, with the IDH-1 inhibitor ivosidenib that has reported interesting results in advanced CCA patients.

Areas covered: Herein, we will critically discuss the current state of the art of ivosidenib in IDH-mutant CCA, especially focusing on efficacy and safety results of recent trials assessing this IDH-1 inhibitor.

Expert opinion: According to the results of phase I studies and the recently published ClarIDHy phase III trial, the IDH-1 inhibitor ivosidenib seems to be associated with a manageable safety profile and interesting antitumor efficacy. In particular, the ClarIDHy showed that ivosidenib treatment reported improved progression-free survival (PFS) compared to placebo in previously treated patients, with median PFS of 2.7 and 1.4 months, respectively. However, several questions remain unanswered and the effective impact of ivosidenib in IDH-mutant CCA remains open.

KEYWORDS:

• Ivosidenib
• cholangiocarcinoma
• claridhy
• targeted therapies
• IDH–1
• intrahepatic cholangiocarcinoma

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewers disclosure

A reviewer on this manuscript has disclosed a conflict of interest (honoraria for lectures, consulting fees, or travel expenses) with Agios, Amgen, Bayer, BMS, HalioDx, Incyte, Merck Serono, MSD, Pierre Fabre Oncologie, Roche, Sanofi, Servier and Viatris. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.