Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

mIDH1 Inhibitor Ivosidenib Improves Progression-Free Survival in Advanced Cholangiocarcinoma

Key clinical point: Ivosidenib significantly improved progression-free survival, compared with placebo, for advanced cholangiocarcinoma.

Major finding: Median progression-free survival was 2.7 months with ivosidenib versus 1.4 months with placebo.

Study details: The phase 3 ClarIDHy study of 185 patients.

Disclosures: ClarIDHy was funded by Agios Pharmaceuticals. Dr. Abou-Alfa reported both personal and institutional relationships with industry. These include advisory /consulting roles and research grants/funding from numerous pharmaceutical companies.


Abou-Alfa GK et al. ESMO 2019, Abstract LBA10-PR.


Treatment of advanced cholangiocarcinoma has been challenging, partly due to lower incidence (and the difficulties in conducting enough large randomized trials), and partly due to biology. Approximately 15% of cholangiocarcinoma tumors exhibit mutations in the protein isocitrate dehydrogenase 1 (IDH1), which plays a key role in the citric acid cycle. Ivosidenib is an inhibitor of IDH1 and FDA-approved for use in patients with acute myelogenous leukemia that harbors IDH1 mutations; therefore, it seems feasible that this drug could be effective for other tumors with IDH1 mutations. In the phase III ClarIDHy trial, Abou-Alfa et al. compared patients with advanced cholangiocarcinoma that harbored IDH1 mutations who received ivosidenib with those that received placebo. While the primary endpoint, progression-free survival, was statistically higher for the treatment group (2.7 months versus 1.4 months), the benefit was modest. Further study in advanced cholangiocarcinoma is of high importance.—Mark A. Klein, MD