Ivosidenib is a small molecule inhibitor of IDH1, which has been approved by the US. FDA for the treatment of acute myeloid leukemia (AML). The mutation rate of IDH1 in cholangiocarcinoma (CCA) is about 15%, so that ivosidenib could be a potential treatment. In phase 3 ClarIDHy trial, IDH1-mutated CCA patients who had received 1-2 prior therapies were randomized in a 2:1 ratio to receive ivosidenib and placebo. Patients in the placebo group were allowed to receive ivosidenib after disease progression. In a total of 185 patients, the median PFS was 2.7 months in the ivosidenib group and 1.4 months in the placebo group (HR 0.37, 95% CI: 0.25-0.54; p < 0.001). The median OS was 10.8 months with ivosidenib and 9.7 months with placebo. After adjusting for the crossover, the median OS of the placebo group was 6.0 months (HR 0.46, 95% CI: 0.28-0.75; p < 0.001). The above results demonstrated that ivosidenib could benefit CCA patients who have an IDH1 mutation.
Annals of Oncology (2019) 30 (suppl_5): v851-v934. 10.1093/annonc/mdz394.