Cabozantinib (Cabometyx) has been approved to treat locally advanced or metastatic differentiated thyroid cancer that has progressed following prior vascular endothelial growth factor receptor-targeted therapy when the patient is ineligible or not responsive to radioactive iodine. Cabozantinib is approved for those ages 12 years and older. Previously, cabozantinib was approved to treat renal cell cancer and hepatocellular cancer.
Cabozantinib is a kinase inhibitor, inhibiting the activity of tyrosine kinases involved in both normal cellular function and pathological processes of cancer cells such as oncogenesis, metastasis, tumor angiogenesis, drug resistance, and maintenance of the tumor microenvironment.
Cabozantinib's efficacy was evaluated in a randomized, double-blind, placebo-controlled, multicenter clinical trial that enrolled 187 individuals-125 received cabozantinib and 62 received placebo. The outcomes were progression-free survival and overall response rate. The trial results showed a statistically significant improvement in progression-free survival for those receiving cabozantinib (11 months versus 1.9 months in those receiving placebo) but not in overall response rate.
The most common adverse effects of cabozantinib treatment were diarrhea, palmar-plantar erythrodysesthesia (also known as hand-foot syndrome, where there is redness, swelling, and pain on the palms and/or soles of the feet), fatigue, hypertension, and stomatitis. Serious adverse effects include perforations and fistulas, thrombotic events, hypertension and hypertensive crisis, diarrhea, palmar-plantar erthrodysesthesia, hepatotoxicity, adrenal insufficiency, proteinuria, osteonecrosis of the jaw, impaired wound healing, reversible posterior leukoencephalopathy syndrome, thyroid dysfunction, and hypocalcemia. While hypocalcemia can occur with any clinical use, it is more likely to happen when cabozantinib is used to treat differentiated thyroid cancer.
Nurses caring for patients prescribed cabozantinib should use a drug database to assess for strong cytochrome P-450 (CYP) 3A4 inhibitors or inducers because cabozantinib is metabolized via the CYP3A4 isoenzyme system. Strong CYP3A4 inhibitors can increase circulating levels of cabozantinib and therefore increase the risk of adverse effects, requiring a dose reduction. Strong CYP3A4 inducers will decrease circulating levels of cabozantinib, requiring a dose increase. Hepatic function should also be assessed, as patients with moderate and severe hepatic impairment require a lower starting dose.
Nurses should teach patients to take the drug at least one hour before or two hours after a meal, as high-fat meals increase the available amount of cabozantinib. The drug should be swallowed whole and not crushed. Nurses should monitor closely for adverse effects, which, depending on their severity, may require a dose reduction. The patient's laboratory values should be monitored carefully for hypocalcemia. Calcium supplementation may be necessary in some patients.
For complete prescribing information for cabozantinib, go to http://www.accessdata.fda.gov/drugsatfda_docs/label/2021/208692s012lbl.pdf.