Cabozantinib Mechanism of Action
1. Inhibits multiple receptor tyrosine kinases (RTKs) that are involved in initiating various intracellular signaling cascades, leading to cell proliferation and/or affecting key processes critical for cell survival and tumor progression (e.g., angiogenesis, metastasis, inhibition of apoptosis), depending on the respective kinase.
2. In medullary thyroid carcinoma cells, multiple tyrosine kinases and pathways are aberrantly activated (e.g., rearranged during transfection [RET] proto‑oncogene mutations are associated with the development of hereditary medullary thyroid carcinoma).
3. In vitro, inhibits the activity of multiple RTKs, including RET; the met proto‑oncogene encoding hepatocyte growth factor receptor (c‑MET); vascular endothelial growth factor receptors (VEGFR)‑1, VEGFR‑2, and VEGFR‑3; stem cell factor receptor (c‑Kit); tropomyosin receptor kinase B (trkB); fms‑like tyrosine kinase 3 (Flt‑3); AXL; and TIE‑2. These RTKs are involved in both normal cellular functions and pathological processes (e.g., tumorigenesis, metastasis, tumor angiogenesis, maintenance of the tumor microenvironment).
Important Notes
1. Cabozantinib should not be taken with food. Swallow cabozantinib capsules whole with a full glass (at least 240 mL) of water. Do not open or crush the capsules. Swallow cabozantinib tablets whole; do not crush the tablets. Avoid grapefruit or grapefruit juice during treatment.
2. If a dose of cabozantinib is missed and it is ≥12 hours before the next scheduled dose, take the missed dose as soon as possible and take the next dose at the scheduled time. If the missed dose is 12 hours before the next scheduled dose, take the next dose at the scheduled time; do not take the missed dose.
3. Breastfeeding should be discontinued during cabozantinib treatment and for 4 months after the last dose.
4. Inform the clinician of current or planned concomitant therapies, including prescription and over‑the‑counter medications, as well as dietary and herbal supplements (e.g., St. John's wort), and any concomitant diseases (e.g., hypertension, bleeding or wound disorders, hepatic impairment).
Cabozantinib Dosage Forms
Cabozantinib capsules (Cometriq): 20 mg (cabozantinib content); 80 mg (cabozantinib content).
Cabozantinib tablets (Cabometyx): 20 mg (cabozantinib content); 40 mg (cabozantinib content); 60 mg (cabozantinib content).
