Cabozantinib

Mechanism of action

✂MET, VEGFR2, RET and KIT tyrosine kinasesCabozantinib

ⓘ The figure shows cabozantinib in the ATP pocket of the human MET kinase; it also blocks VEGFR2.

Cabozantinib inhibits several tyrosine kinases, most potently VEGFR2, then MET, RET and KIT. Blocking VEGFR2 cuts angiogenesis, blocking MET and KIT reaches growth signals of the tumour cell, and RET blockade fits its use in medullary thyroid cancer.

1. Blocks VEGFR2, MET, RET and KIT kinases
2. VEGFR2: angiogenesis stops; MET and KIT: tumour signals cut
3. RET: activity in medullary thyroid cancer

Indications

• Advanced renal cell carcinoma, alone or first line with nivolumab. Renal cell carcinoma →
• Hepatocellular carcinoma previously treated with sorafenib. Hepatocellular carcinoma →
• Progressive metastatic medullary thyroid cancer. Medullary thyroid carcinoma →
• Differentiated thyroid cancer that no longer responds to radioactive iodine, after VEGFR-targeted therapy. Thyroid cancer (papillary) →
• Previously treated, metastatic well-differentiated neuroendocrine tumours of the pancreas or other organs. Pancreatic neuroendocrine tumours (VIPoma, glucagonoma, somatostatinoma, non-functioning) →

Adverse effects

Common

• Diarrhoea, nausea, vomiting, constipation
• Fatigue and weight loss
• Hand-foot skin reaction (red, painful, peeling palms and soles)
• Hypertension
• Mouth sores, taste changes, change of hair colour

Contraindications

• Recent history of serious bleeding

Key interactions

Strong CYP3A4 inhibitors (clarithromycin, itraconazole, ketoconazole, ritonavir) and grapefruit

Raise cabozantinib exposure.

Strong CYP3A4 inducers (rifampicin, carbamazepine, phenytoin, St John's wort)

Lower its levels and can make it fail.

Anticoagulants and antiplatelet drugs

Add to its bleeding risk.

What is monitored

• Blood pressure regularly
• Signs of bleeding, perforation or thrombosis
• Dental examination before and during treatment
• Laboratory tests as ordered

Administration and safety

• Oral, once daily on an empty stomach, away from meals; swallowed whole, not split, crushed or opened.
• Capsule and tablet products are approved for different cancers: check that the form dispensed matches the order.
• Grapefruit, its juice and St John's wort are avoided because they change its levels.
• Stopped before planned surgery or dental surgery and restarted only when the wound has healed, as the doctor directs.

Pregnancy and breastfeeding

Avoid in pregnancy. Can harm the fetus: a pregnancy test is done before starting, effective contraception is used during treatment and for a time afterwards (by women and by men with partners who could conceive), and breastfeeding is avoided.

Nursing care

• Measure blood pressure at every visit and teach home monitoring if ordered.
• Teach to report bleeding, black stools, vomiting blood, severe abdominal pain, chest pain or stroke symptoms at once.
• Advise a dental check before starting and to tell any dentist or surgeon about the drug.
• Confirm a negative pregnancy test before the first dose and teach contraception during treatment and afterwards.

Pharmacokinetics

Absorption

Oral, once daily, on an empty stomach.

Metabolism

Liver, CYP3A4.

Half-life

Long: about 99 hours.

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Connections

← Back to the class: VEGFR multikinase inhibitors

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Cabozantinib: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2025); Cabozantinib-S-Malate - NCI (National Cancer Institute, 2025); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.