Physicians treating previously treated locally advanced or metastatic cholangiocarcinoma with isocitrate dehydrogenase 1 (IDH1) mutations now have a treatment option for their patients.

Ivosidenib, an IDH1 inhibitor, has been accorded US Food and Drug Administration (FDA) approval as the first targeted therapy for this indication. This approval is based on the ClarIDHy trial, which showed a significant improvement in the progression-free survival of ivosidenib-treated patients.

• Dosage and administration: 500 mg orally once daily with / without food until disease progression occurs or toxicity is unacceptable. Avoid a high-fat meal
• Adverse effects: Fatigue, nausea, abdominal pain, diarrhea, cough, decreased appetite, ascites, vomiting, anemia, rash, decrease in hemoglobin and increase in bilirubin and aspartate aminotransferase (AST)
• Warning and Precautions: QTc interval prolongation, Guillain-Barré syndrome. The FDA has also issued a black box warning about the risk of differentiation syndrome with ivosidenib. Some symptoms of differentiation syndrome are fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension organ dysfunction. Management includes steroids and hemodynamic monitoring until symptoms improve.

Ivosidenib has been earlier approved as first-line treatment for newly-diagnosed acute myeloid leukemia (AML) with a susceptible IDH1 mutation in patients aged ≥75 years or those in whom comorbidities prevent the use of intensive induction chemotherapy and patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible IDH1 mutation.

(Source: Medscape & US FDA, August 26, 2021)