Initial US Approval:
2012
Key Clinical Studies:
CABINET (NCT03375320)
Drug Class/Description:
Kinase inhibitor
Indications and Usage:
CABOMETYX is a kinase inhibitor indicated for the treatment of
- patients with advanced renal cell carcinoma (RCC).
- patients with advanced renal cell carcinoma, as a first-line treatment in combination with nivolumab.
- patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib.
- adult and pediatric patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible.
- adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated pancreatic neuroendocrine tumors (pNET).
- adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated extra-pancreatic neuroendocrine tumors (epNET).
Dosage and Administration:
- Do NOT substitute CABOMETYX tablets with cabozantinib capsules.
- Administer on an empty stomach at least 1 hour before or at least 2 hours after eating.
- Stop treatment with CABOMETYX at least 3 weeks prior to scheduled surgery, including dental surgery.
- Recommended Dose:
- 60 mg orally, once daily.
- 40 mg orally, once daily, administered in combination with nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks.
- 40 mg orally, once daily, in pediatric patients 12 years of age and older with bodyweight less than 40 kg.
Dosage Forms and Strengths:
Tablets: 60 mg, 40 mg, 20 mg.
Contraindications:
None.
Warnings and Precautions:
- Hemorrhage: Do not administer CABOMETYX if recent history of hemorrhage.
- Perforations and Fistulas: Monitor for symptoms. Discontinue CABOMETYX for Grade 4 fistula or perforation.
- Thrombotic Events: Discontinue CABOMETYX for myocardial infarction or serious venous or arterial thromboembolic events.
- Hypertension and Hypertensive Crisis: Monitor blood pressure regularly. Interrupt for hypertension that is not adequately controlled with anti-hypertensive therapy. Discontinue CABOMETYX for hypertensive crisis or severe hypertension that cannot be controlled with anti-hypertensive therapy.
- Diarrhea: May be severe. Interrupt CABOMETYX until diarrhea resolves or decreases to ≤Grade 1, resume at reduced dose. Recommend standard antidiarrheal treatments.
- Palmar-Plantar Erythrodysesthesia (PPE): Interrupt CABOMETYX treatment until PPE resolves or decreases to Grade 1.
- Hepatotoxicity: When used in combination with nivolumab, higher frequencies of Grade 3 and 4 ALT and AST elevation may occur than with CABOMETYX alone. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider withholding CABOMETYX and/or nivolumab, initiating corticosteroid therapy, and/or permanently discontinuing the combination for severe or life-threatening hepatotoxicity.
- Adrenal Insufficiency: When used in combination with nivolumab, primary or secondary adrenal insufficiency may occur. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold CABOMETYX and/or nivolumab depending on severity.
- Proteinuria: Monitor urine protein. Interrupt CABOMETYX until proteinuria resolves to ≤Grade 1, resume CABOMETYX at a reduced dose. Discontinue for nephrotic syndrome.
- Osteonecrosis of the jaw (ONJ): Withhold CABOMETYX for at least 3 weeks prior to invasive dental procedures and for development of ONJ.
- Impaired Wound Healing: Withhold CABOMETYX for at least 3 weeks before elective surgery. Do not administer for at least 2 weeks following major surgery and adequate wound healing. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established.
- Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Discontinue CABOMETYX.
- Thyroid Dysfunction: Monitor thyroid function before and during treatment with CABOMETYX.
- Hypocalcemia: Withhold CABOMETYX and resume at reduced dose upon recovery or permanently discontinue CABOMETYX depending on severity.
- Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception.
Adverse Reactions:
The most common (≥20%) adverse reactions are:
- as a single agent: diarrhea, fatigue, PPE, decreased appetite, hypertension, nausea, vomiting, weight decreased, constipation.
- in combination with nivolumab: diarrhea, fatigue, hepatotoxicity, PPE, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.
Drug Interactions:
- Strong CYP3A4 inhibitors: Reduce the CABOMETYX dosage if coadministration cannot be avoided.
- Strong or moderate CYP3A4 inducers: Increase the CABOMETYX dosage if coadministration cannot be avoided.
Use in Specific Populations:
- Hepatic Impairment: Reduce the CABOMETYX dosage for patients with moderate hepatic impairment. Avoid in patients with severe hepatic impairment.
- Lactation: Advise not to breastfeed.
- Pediatric Use: Monitor open growth plates in adolescent patients. Consider interrupting or discontinuing CABOMETYX if abnormalities occur.
Adapted From:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208692s000lbl.pdf
Every health-care provider should make their own determination regarding specific safe and appropriate patient care practices, including drug dosages and indications. The provider should always consult the most recent prescribing/product information. FDA Focus information is not guaranteed to be accurate, complete, or current. JADPRO and its editors, authors, reviewers, and commentators cannot be held responsible for any liability incurred as a consequence of the application of any of the information listed within.
