Cabozantinib
Overview
Cabozantinib is an orally administered small‑molecule multi‑kinase inhibitor that targets several receptor tyrosine kinases involved in tumour growth, angiogenesis, metastasis, and resistance pathways, including c‑MET, vascular endothelial growth factor receptors, AXL, RET, FLT3, KIT, and related kinases. By inhibiting these receptors, cabozantinib interferes with tumour blood vessel formation and tumour cell signalling, which can slow the progression of certain advanced cancers. Its mechanism of action underlies its use in multiple advanced solid tumour types where angiogenesis and kinase‑driven signalling play key roles in disease biology. Cabozantinib’s broad spectrum of kinase targets distinguishes it from single‑target agents and supports activity across cancer subtypes with varying molecular drivers. It is administered orally, allowing outpatient management, but requires careful clinical oversight because of potential effects on the liver, blood pressure, cardiac conduction, and gastrointestinal tract. Cabozantinib has become a well‑established targeted therapy for selected advanced malignancies where systemic disease control with kinase inhibition is clinically appropriate.
Background and Date of Approval
Cabozantinib was developed as a multi‑targeted tyrosine kinase inhibitor with anti‑tumour activity in preclinical models and clinical trials. The United States Food and Drug Administration first approved cabozantinib under the brand name Cometriq for the treatment of progressive metastatic medullary thyroid cancer in November 2012. The tablet formulation under the name Cabometyx received FDA approval on 25 April 2016 for the treatment of advanced renal cell carcinoma after prior therapy. The FDA expanded approvals over time, including on 14 January 2019 for hepatocellular carcinoma previously treated with sorafenib and on 17 September 2021 for locally advanced or metastatic differentiated thyroid cancer following prior VEGFR‑targeted therapy. The European Medicines Agency has similarly authorised cabozantinib for comparable cancer indications, with a positive opinion for expanded indications including neuroendocrine tumours issued on 19 June 2025. These regulatory milestones were supported by pivotal clinical trials demonstrating improvements in progression‑free and overall survival in the respective disease settings.
Uses
Cabozantinib is indicated for the treatment of adults with progressive metastatic medullary thyroid cancer. It is also indicated for adults with advanced renal cell carcinoma, including as monotherapy after previous anti‑angiogenic therapy and in combination with immune therapies in first‑line settings. In addition, cabozantinib is used for adults with hepatocellular carcinoma who have been previously treated with sorafenib and for locally advanced or metastatic differentiated thyroid cancer that has progressed following prior VEGFR‑targeted therapy. These indications reflect its utility across multiple tumour types driven by kinase‑dependent pathways and resistant to earlier lines of therapy.
Administration
Cabozantinib is administered orally in tablet form. The typical starting dose for advanced renal cell carcinoma, hepatocellular carcinoma, and differentiated thyroid cancer is 60 mg once daily, taken at least one hour before or two hours after a meal to ensure consistent absorption. Dose adjustments are often necessary in patients who experience significant toxicities or in those with hepatic impairment, which can alter drug metabolism. Treatment is generally continued until disease progression or unacceptable toxicity, with routine assessments of liver function, blood pressure, and overall tolerability to guide ongoing dosing decisions.
Side Effects
Frequent side effects observed with cabozantinib include diarrhea, fatigue, decreased appetite, nausea, palmar‑plantar erythrodysesthesia (hand‑foot syndrome), hypertension, weight loss, and taste changes. Patients may also experience hair colour changes, stomatitis, constipation, or headache. The severity of these effects varies among individuals, and many are manageable with supportive care, dose modifications, and close medical supervision.
Warnings
Cabozantinib carries risks of serious adverse events including severe hepatotoxicity, gastrointestinal perforation and fistulas, arterial and venous thrombotic events, and severe hypertension. Cardiac dysfunction and QT interval prolongation have been reported, and rare neurological syndromes may occur. It can also cause fetal harm when administered during pregnancy, and effective contraception is advised. Treatment interruption or discontinuation is necessary in cases of life‑threatening toxicities.
Precautions
Before initiating cabozantinib, baseline evaluations including liver function tests, blood pressure assessment, and cardiac status are essential. Cabozantinib is metabolised principally via hepatic pathways, and concomitant use of strong CYP3A4 inhibitors or inducers may necessitate dose adjustments. Special caution is required in patients with pre‑existing liver disease or cardiovascular risk factors. Use during pregnancy and breastfeeding is not recommended due to potential teratogenic effects. Regular monitoring and appropriate adjustments help mitigate serious complications.
Expert Tips
Patient selection for cabozantinib should consider tumour type, prior therapies, organ function, and comorbidities. Baseline and periodic liver and cardiovascular assessments are crucial, and counselling patients on adherence, administration timing relative to meals, and prompt reporting of symptoms can improve safety. Ongoing monitoring of liver enzymes, blood pressure, and signs of gastrointestinal or cardiovascular toxicity will guide clinical decisions. Coordination with supportive care and management of overlapping toxicities from combination regimens enhances tolerability and therapeutic outcomes.