Cabometyx (cabozantinib)

A targeted therapy pill that blocks multiple growth signals cancer cells use to survive and spread. Being studied in adrenocortical carcinoma after standard treatments have stopped working.

Cabozantinib blocks multiple growth-promoting proteins in cancer cells, including c-MET, VEGFR2, and AXL. These proteins normally help cancer cells grow, spread, and form new blood vessels. By blocking them all at once, the drug slows tumor growth and can help shrink existing tumors.

The most common side effect is diarrhea. On the Cabometyx label it affected 62% of people across studies and 74% in the main kidney cancer trial^[2]. Other frequent effects include mouth sores, nausea, decreased appetite, and hand-foot syndrome (redness and pain in palms and soles). Most side effects are manageable, though some patients require dose reductions.

Cabozantinib is taken orally as a tablet once daily, typically starting at 60 mg. It must be taken on an empty stomach, at least 1 hour before or at least 2 hours after eating^[2]. Tablets should be swallowed whole. Avoid grapefruit as it interferes with drug metabolism.

Cabozantinib is currently in phase 2 clinical trials for Adrenocortical Carcinoma. It has not yet received FDA approval.

As Cabometyx, cabozantinib is FDA-approved for advanced kidney cancer, liver cancer previously treated with sorafenib, differentiated thyroid cancer after other targeted drugs, and some neuroendocrine tumors. As Cometriq, it is approved for medullary thyroid cancer^[2]. Its use in adrenocortical carcinoma is investigational, currently in Phase 2 trials.

In a Phase 2 trial at MD Anderson Cancer Center, cabozantinib showed promising activity, with 13 of 18 patients (72%) free of cancer growth at 4 months (Lancet Oncology, 2024). Phase 2 trials are now testing it with the immunotherapy drugs cemiplimab (NCT06900595) and pembrolizumab (NCT06006013).

Cabozantinib simultaneously inhibits several growth-promoting proteins including c-MET, VEGFR2, RET, and AXL. By blocking multiple pathways at once, it addresses several mechanisms cancer cells use to grow and spread.

Cabometyx tablets must be taken on an empty stomach, at least 1 hour before or at least 2 hours after eating. Cometriq capsules have a different rule, no food for 2 hours before and 1 hour after. Grapefruit should be avoided as it interferes with drug metabolism. Tablets should be swallowed whole.

Diarrhea is the most common side effect. On the Cabometyx label it affected 62% of people across studies and 74% in the main kidney cancer trial. Mouth sores, nausea, decreased appetite, and hand-foot syndrome (redness and pain in palms and soles) are also frequent. Most are manageable with dose reductions.