Cabozantinib is a targeted therapy, specifically a multi-kinase inhibitor. This oral medication functions as an anti-cancer drug by interfering with specific pathways involved in tumor growth and progression. It blocks signals within cancer cells, helping to slow or stop the disease’s advancement, and is utilized to treat various advanced cancers.
Conditions Treated by Carbozantinib
Cabozantinib is approved for treating several types of advanced cancers. It is used in advanced renal cell carcinoma (RCC), a type of kidney cancer, often after other treatments have been attempted. Cabozantinib has shown improved progression-free and overall survival for patients with advanced RCC.
The medication is also approved for hepatocellular carcinoma (HCC), a form of liver cancer, particularly for patients previously treated with sorafenib. In clinical trials, cabozantinib improved overall survival to a median of 10.2 months compared to 8 months in the placebo group for HCC patients. It also prolonged progression-free survival.
Furthermore, cabozantinib is indicated for differentiated thyroid cancer (DTC) that has progressed following prior therapy and is radioactive iodine-refractory. This includes follicular and papillary thyroid cancers that do not respond to radioactive iodine treatment. Cabozantinib was initially approved by the U.S. Food and Drug Administration (FDA) in 2012 for the first-line treatment of medullary thyroid cancer.
Beyond these approved indications, cabozantinib is being investigated in clinical trials for other malignancies, including lung cancer, prostate cancer, and neuroblastoma. Its ability to target multiple pathways makes it a candidate for various tumor types.
How Carbozantinib Works
Cabozantinib operates as a multi-targeted tyrosine kinase inhibitor (TKI). It blocks the activity of several proteins, known as receptor tyrosine kinases (RTKs), which are overexpressed in cancer cells and their surrounding environment. These RTKs play roles in tumor growth, the formation of new blood vessels (angiogenesis), and the spread of cancer (metastasis). By inhibiting these targets, cabozantinib disrupts the signaling pathways tumors rely on for survival and proliferation.
A primary target of cabozantinib is MET (mesenchymal-epithelial transition factor), a receptor involved in cell growth, survival, and motility. Blocking MET signaling inhibits tumor cell proliferation and invasion.
Cabozantinib also inhibits Vascular Endothelial Growth Factor Receptor 2 (VEGFR2). VEGFR2 is a component in angiogenesis, the process by which tumors create new blood vessels to supply themselves with nutrients and oxygen. By disrupting VEGFR2, cabozantinib can reduce tumor blood supply, leading to decreased tumor growth.
Another target is AXL (anexelekto), a receptor tyrosine kinase implicated in cancer cell survival, drug resistance, and metastasis. By inhibiting AXL, cabozantinib can help overcome some resistance mechanisms and suppress tumor progression. Cabozantinib also inhibits other RTKs such as RET, KIT, and FLT3.
Managing Treatment with Carbozantinib
Cabozantinib is an oral medication, taken as tablets (Cabometyx) or capsules (Cometriq), with specific instructions for administration. Cabometyx tablets are taken once daily on an empty stomach, at least one hour before or two hours after eating. Cometriq capsules, used for medullary thyroid cancer, should be taken without food, ensuring a two-hour gap before and one hour after eating. Swallow both tablets and capsules whole, without crushing, chewing, or opening them.
Patients may experience various side effects. Common side effects include fatigue (affecting up to 79% of patients) and diarrhea (over 70%). Other frequent side effects include nausea, high blood pressure (hypertension), mouth sores (stomatitis), decreased appetite, and hand-foot syndrome, characterized by redness and pain in the palms and soles. These are generally manageable with supportive care and dose adjustments.
Managing these side effects often involves proactive measures and close communication with healthcare providers. For diarrhea, maintaining hydration is important, and anti-diarrheal medications may be prescribed. Hand-foot syndrome can be managed with skin care, including moisturizers, and sometimes requires dose adjustments. Blood pressure should be regularly monitored, and medication may be needed to control hypertension. If side effects become severe, the dosage of cabozantinib can be reduced stepwise, for example, from 60 mg to 40 mg, then to 20 mg daily.
Regular monitoring is important, including blood tests to check liver enzyme levels, blood counts, and kidney function. Healthcare providers will also check blood pressure. It is important to inform your doctor about any other medications being taken, as drug interactions can occur. Adherence to the prescribed treatment plan, including dose modifications, is important for optimizing outcomes and managing any adverse effects effectively.