Oncology Drug Reference Sheet: Cabozantinib

Of note: cabozantinib is also marketed as Cometriq^® for the treatment of patients with progressive, metastatic medullary thyroid cancer. Cometriq should not be substituted for Cabometyx. 

Category/Class

Multitargeted tyrosine kinase inhibitor (including VEGFR-1) 

Indication

Current approved indications are for advanced renal cell carcinoma and hepatocellular carcinoma following sorafenib. 

Dosing

Administer 60 mg orally once daily without food. Doses should be withheld for any intolerable grade 2 adverse event, any grade 3 or 4 event, or osteonecrosis of the jaw. Upon resolution, cabozantinib can be restarted following a dose-reduced regimen. It should be stopped at least 28 days prior to scheduled surgery and not resumed until adequate wound healing.                            

Administration

Cabozantinib is taken orally, and patients should avoid food and drink for two hours prior to dosing and one hour after. Instruct patients to take the tablets whole with water and not to crush or manipulate the pills in any way (https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208692s000lbl.pdf).      

Adverse Reactions 

Most common side effects are diarrhea, fatigue, decreased appetite, weight loss, nausea and vomiting, palmar-plantar erythrodysesthesia, mouth pain, and hypertension. Less common but severe and fatal effects are thrombotic events (7%), hemorrhage (5%), and perforations and fistulas (1%). Osteonecrosis of the jaw is rare (< 1%) but considered serious, and the drug should be discontinued if encountered (https://voice.ons.org/news-and-views/fda-approves-cabozantinib-for-hepatocellular-carcinoma).  

Nursing Considerations

• Watch for drug-drug and drug-food interactions with other CYP3A4 inhibitors or inducers.
• Assess patients for oral adherence.
• Discontinue cabozantinib at least 28 days prior to planned surgery because of wound complication reports.
• Ensure blood pressure is controlled prior to therapy initiation and monitored throughout therapy.

Drug-Drug and Drug-Food Interactions  

• Avoid using cabozantinib concurrently with strong CYP3A4 inhibitors, including grapefruit, or consider reducing the dosing.
• Avoid using cabozantinib concurrently with strong CYP3A4 inducers (https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208692s000lbl.pdf), including St. John’s wort, or consider increasing the dosing.   

Patient Education

• Store at room temperature out of reach of children and pets.
• Avoid grapefruit juice and supplements with St. John’s wort.
• Report any signs of bleeding, diarrhea, and thrombosis, including swelling or pain in limbs.
• Avoid pregnancy while on therapy and for four months after final dose. Do not breastfeed during treatment and for four months after the final dose.

Gero-Oncology Considerations

Because many older adults have comorbidities or are prescribed other pharmacologic agents, polypharmacy and concomitant medications should be considered. No overall differences in safety or effectiveness was seen in clinical trials between patients aged 65 or older and younger patients. 

Safe Handling

Cabozantinib is a hazardous drug that has been demonstrated to be embryotoxic. Safe handling recommendations (https://www.cdc.gov/niosh/docs/2016-161/pdfs/2016-161.pdf) should be adhered to during all administration and handling activities.

Patient Assistance

Patient assistance may be available through the EASE program (https://cabometyx.com/financial-support). To find out which patients may qualify, call 844-900-EASE.