Sept 19, 2021: The Food and Drug Administration approved Ivosidenib (Tibsovo, Servier Pharmaceuticals LLC) for adult patients with previously treated, locally advanced or metastatic cholangiocarcinoma with an isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test.
Today, the FDA also approved the Oncomine Dx Target Test (Life Technologies Corporation) as a companion diagnostic device to aid in selecting patients with cholangiocarcinoma for treatment with ivosidenib.
Ivosidenib was investigated in a randomised (2:1), multicenter, double-blind, placebo-controlled clinical trial (Study AG120-C-005, NCT02989857) of 185 adult patients with locally advanced or metastatic cholangiocarcinoma with an IDH1 mutation. The patient’s disease must have progressed following at least one, but not more than two prior regimens, including at least one gemcitabine- or 5-flurouracil-containing regimen. Patients were randomised to receive either ivosidenib 500 mg orally once daily or matched placebo until disease progression or unacceptable toxicity.
The primary efficacy endpoint was progression-free survival (PFS) as determined by independent review committee according to RECIST 1.1. The trial demonstrated a statistically significant improvement in PFS for patients randomised to ivosidenib (HR 0.37; 95 percent CI: 0.25, 0.54; p<0.0001). The analysis of OS was not significant (0.79; 95 percent CI: 0.56, 1.12; p=0.093); 70 percent of patients randomised to placebo had crossed over to receive ivosidenib after radiographic disease progression.
The most common adverse reactions (≥15 percent ) in patients with cholangiocarcinoma were fatigue, nausea, abdominal pain, diarrhea, cough, decreased appetite, ascites, vomiting, anemia, and rash.
The recommended ivosidenib dosage for cholangiocarcinoma is 500 mg orally once daily with or without food until disease progression or unacceptable toxicity.