General Information

Cometriq (cabozantinib) is a pan-tyrosine kinase inhibitor. These receptor tyrosine kinases are involved in both normal cellular function and pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of the tumor microenvironment.

Cometriq is specifically approved for the treatment of progressive, metastatic medullary thyroid cancer.

Cometriq is supplied as a capsule for oral administration. The recommended daily dose of Cometriq is 140 mg (one 80-mg and three 20-mg capsules). Cometriq should not be administered with food. Patients should not to eat for at least 2 hours before and at least 1 hour after taking Cometriq. Continue treatment until disease progression or unacceptable toxicity occurs.

Mechanism of Action

Cometriq (cabozantinib) inhibits the tyrosine kinase activity of RET, MET, VEGFR-1, -2 and -3, KIT, TRKB, FLT-3, AXL, and TIE-2. These receptor tyrosine kinases are involved in both normal cellular function and pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of the tumor microenvironment.

Side Effects

Adverse events associated with the use of Cometriq may include, but are not limited to, the following:

• diarrhea
• stomatitis
• palmar-plantar erythrodysesthesia syndrome
• decreased weight
• decreased appetite
• nausea
• fatigue
• oral pain
• hair color changes
• dysgeusia
• hypertension
• abdominal pain
• constipation

Clinical Trial Results

The FDA approval of Cometriq was based on an international, multi-center, randomized, double-blind, controlled trial in 330 subjects with metastatic medullary thyroid carcinoma (MTC). The subjects were required to have evidence of actively progressive disease within 14 months prior to study entry confirmed by an Independent Radiology Review Committee or the treating physician. Subjects were randomized to receive Cometriq 140 mg or placebo orally once daily, without food, until disease progression or until intolerable toxicity. Randomization was stratified by age (< 65 years vs. > 65 years) and prior use of a tyrosine kinase inhibitor. The main efficacy outcome measures were progression-free survival (PFS), objective response (OR), and response duration using modified RECIST criteria. A statistically significant prolongation in PFS was demonstrated among the Cometriq-treated arm compared to placebo (p <0.0001), with median PFS times of 11.2 months and 4.0 months in the Cometriq and placebo arms, respectively. Partial responses were observed only among subjects in the Cometriq arm (27% vs. 0; p<0.0001). The median duration of objective responses was 14.7 months for subjects treated with Cometriq. There was no statistically significant difference in overall survival between the treatment arms at the planned interim analysis.