Cabozantinib (CABOMETYX)

Renal cell carcinoma, advanced or metastatic

Hepatocellular carcinoma, advanced or metastatic

Thyroid carcinoma, advanced or metastatic

Renal cell carcinoma, advanced or metastatic

• Dose – Oral (Monotherapy): 60 mg once daily continuously until disease progression or unacceptable toxicity
• Dose – Oral (in combination with nivolumab): 40 mg once daily continuously until disease progression or unacceptable toxicity

Hepatocellular carcinoma, advanced or metastatic

• Dose – Oral: 60 mg once daily continuously until disease progression or unacceptable toxicity

Thyroid carcinoma, advanced or metastatic

• Dose – Oral: 60 mg once daily continuously until disease progression or unacceptable toxicity

Available as 20 mg, 40 mg, and 60 mg film-coated tablets. Tablets should NOT be crushed or broken. Tablets contain lactose. Store at room temperature.

Multi-targeted TKI (tyrosine kinase inhibitor) which includes action as a Vascular Endothelial Growth Factor (VEGF) Inhibitor

Take an empty stomach at least 1 hour before or at least 2 hours after a meal

If a dose is missed, patients should be instructed to take it as soon as they can if it is within 12 hours of the missed dose. If it is over 12 hours since the missed dose, patients should skip the missed dose and resume with the next scheduled dose.

Common: Hypothyroidism, Diarrhea, Nausea, Stomatitis, Fatigue, Anorexia, Hypocalcemia, Hypomagnesemia, Hand-foot skin reaction, Rash, Hypertension.

Less Common: Hemorrhage, Gastrointestinal fistula or perforation, Mucositis, Fistula, non-gastrointestinal, Hepatic failure, Wound complications, Hypokalemia, Osteonecrosis of the jaw, Arterial aneurysm or rupture, Hypertensive crisis, Reversible posterior leukoencephalopathy syndrome, Pulmonary or venous thromboembolism.

The adverse effects listed above are not exhaustive. Please refer to the relevant product monograph for full details.

Baseline before treatment: CBC & differential, platelets, sodium, potassium, magnesium, phosphate, creatinine, total protein, albumin, bilirubin, INR, ALT, alkaline phosphatase, urine analysis, uric acid, TSH, blood pressure.

During treatment: CBC & differential and platelets, urine analysis, creatinine, uric acid, ALT, bilirubin, blood pressure. TSH every other cycle or if clinically indicated.

If clinically indicated: MUGA scan or echocardiogram.

Note: Additional monitoring is required for nivolumab if being used in combination.

• This drug can impact or be impacted by metabolic enzymes for absorption and excretion. Many drugs can also affect or be affected by these enzymes, so please consult with pharmacy to assess for interactions.
• May increase the risk for QT interval prolongation. Avoid concurrent therapy with drugs associated with QTc prolongation and/or Torsades de pointes, if possible. If unavoidable, monitor for QT prolongation or cardiac arrhythmias.
• Avoid grapefruit, grapefruit juice, Seville oranges, or Seville orange juice.
• Current drug interaction databases should be consulted for more information.

• Avoid in pregnancy and lactation.
• Hand-foot skin reaction (HFSR) has been reported with cabozantinib and usually appears during the first eight weeks of treatment. Treatment with urea cream may be considered for prophylaxis or improvement of HFSR grade in VEGF treated patients.
• Hypertension is common with VEGF inhibitors. Monitor blood pressure closely and manage with antihypertensives and dose hold/reductions. Hypertension should be well controlled prior to starting cabozantinib.
• Osteonecrosis of the jaw - Events of osteonecrosis of the jaw (ONJ) have been observed with cabozantinib.  An oral examination should be performed prior to initiation of cabozantinib and periodically during therapy. Patients should be advised regarding oral hygiene practice. For invasive dental procedures, cabozantinib treatment should be held at least 28 days prior to scheduled surgery, if possible.
• Impaired wound healing is associated with VEGF inhibitors, drug may need to be held and restarted if patient requires surgery, discuss with team.

BC Cancer. BC Cancer Drug Manual. Cabozantinib. Vancouver, British Columbia: BC Cancer Agency. Available at http://www.bccancer.bc.ca/drug-database-site/Drug%20Index/Cabozantinib_monograph.pdf . Updated January 1, 2022. Accessed January 22, 2024.

Lexicomp. Cabozantinib Monograph. In: Lexi-Drugs. Hudson, Ohio: Lexi-Comp, Inc. Available at: https://online-lexi-com.qe2a-proxy.mun.ca/lco/action/doc/retrieve/docid/patch_f/4045782?cesid=5ycCXITffq8&searchUrl=%2Flco%2Faction%2Fsearch%3Fq%3Dcabozantinib%26t%3Dname%26acs%3Dtrue%26acq%3Dcabman. Updated January 24, 2024. Accessed January 28, 2024.

Cancer Care Ontario. Cabozantinib Monograph. Drug Formulary. Toronto, Ontario: Cancer Care Ontario. Available at: https://www.cancercareontario.ca/en/drugformulary/drugs/monograph/60461. Updated March 2022. Accessed January 22, 2024.Ipsen Biopharmaceuticals Inc. CABOMETYX® product monograph. Mississauga, Ontario. Updated Oct 6, 2021.