Clinical Utility of Ivosidenib in the Treatment of IDH1-Mutant Cholangiocarcinoma: Evidence To Date

Ivosidenib is an isocitrate dehydrogenase 1 (IDH1) inhibitor that is FDA approved for patients with IDH1 mutation and acute myeloid leukemia and previously treated locally advanced or metastatic cholangiocarcinoma. In the Phase III trial ClarIDHy ivosidenib improved progression-free survival, 2.7 months versus 1.4 months (p < 0.0001) and overall survival (OS), median OS was 10.8 months for ivosidenib and 9.7 months for the placebo arm (p = 0.06) for patients with previously treated and IDH1 mutated cholangiocarcinoma. In this review article, we will address the mechanism of action of ivosidenib and data from early trials and safety from the randomized trial in cholangiocarcinoma. As a conclusion, future perspectives of IDH1 inhibition in IDH1 mutated tumors and possible strategies of sequencing and combinations will be reviewed and discussed.