FDA Approves Ivosidenib for Bile Duct Cancer

Sharon Worcester

August 26, 2021

The Food and Drug Administration (FDA) has approved ivosidenib (Tibsovo) for the treatment of adults with previously treated locally advanced or metastatic IDH1-mutated cholangiocarcinoma (CCA), a rare, aggressive cancer of the bile ducts within and outside of the liver.

The isocitrate dehydrogenase-1 (IDH1) inhibitor is the first targeted therapy approved for IDH1-mutated CCA, which is diagnosed in about 8000 people in the United States each year.

The drug was previously approved as monotherapy for adults with IDH1-mutated relapsed or refractory acute myeloid leukemia (AML) and adults with AML who are aged 75 years and older or who have comorbidities that preclude the use of intensive induction chemotherapy.

"Before today's approval of [ivosidenib], there were no approved targeted therapies available to cholangiocarcinoma patients harboring the IDH1 mutation, and limited chemotherapy options available to patients with advanced disease," Stacie Lindsey, CEO of the Cholangiocarcinoma Foundation, said in a press statement released by Servier Pharmaceuticals, the drug's maker. "This approval brings new hope to the cholangiocarcinoma community and we are excited that this much-needed new therapeutic option is being made available to patients."

The new approval was based on findings from the randomized, phase 3 ClarIDHy trial in which 70.5% of patients in the placebo group crossed over to ivosidenib at the time of progression as permitted by the study protocol.

The primary efficacy endpoint was progression-free survival (PFS); the trial demonstrated a statistically significant improvement in PFS for patients randomized to ivosidenib (HR, 0.37; P < .0001).

Median overall survival was 10.3 months in the ivosidenib group versus 7.5 months in the placebo group, but was not statistically significant.

Common adverse reactions were fatigue, nausea, abdominal pain, diarrhea, cough, decreased appetite, ascites, vomiting, anemia, and rash. However, the agent carries a black box warning about the risk of differentiation syndrome, which some treated patients with AML have experienced.

Symptoms of differentiation syndrome may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, and hepatic, renal, or multi‑organ dysfunction. Corticosteroid therapy and hemodynamic monitoring until symptom resolution are recommended when differentiation syndrome is suspected.

The recommended ivosidenib dosage for previously treated IDH1-mutated cholangiocarcinoma is 500 mg orally once daily with or without food until disease progression or unacceptable toxicity.

Sharon Worcester is an award-winning medical journalist at MDedge News, part of the Medscape Professional Network.

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