Clin Cancer Res. 2022 Mar 8:clincanres.4462.2021. doi: 10.1158/1078-0432.CCR-21-4462. Online ahead of print.
ABSTRACT
On August 25, 2021, the FDA approved ivosidenib for the treatment of adult patients with unresectable locally advanced or metastatic hepatocellular isocitrate-dehydrogenase-1 (IDH1) mutated cholangiocarcinoma (CCA) as detected by an FDA-approved test with disease progression after 1-2 prior lines of systemic therapy for advanced disease. The approval was based on data from Study AG120-C-005 (ClarIDHy), a double-blind placebo-controlled trial which randomly allocated (2:1) patients to receive either ivosidenib or placebo. Independently-assessed progression free survival (PFS) was the primary endpoint. With a median follow up of 6.9 months, the hazard ratio for PFS was 0.37 (95% confidence interval 0.25, 0.54, p< 0.0001). Overall survival (OS) was the key secondary endpoint. At the final analysis of OS, with 70.5% patients in the placebo arm receiving ivosidenib post disease progression, a non-statistically significant improvement in the ivosidenib arm with a HR = 0.79 (95% CI: 0.56, 1.12) and median OS of 10.3 months (95% CI 7.8, 12.4) and 7.5 months (95% CI 4.8, 11.1) in the ivosidenib and placebo arms respectively were reported. Adverse reactions occurring in >20% of patients receiving ivosidenib were fatigue/asthenia, nausea, diarrhea, abdominal pain, ascites, vomiting, cough, and decreased appetite. Adverse reactions occurring in >20% of patients receiving placebo were fatigue/asthenia, nausea, abdominal pain, and vomiting. This is the first approval for the subset of patients with CCA harboring an IDH1 mutation.
PMID:35259259 | DOI:10.1158/1078-0432.CCR-21-4462
