Cabometyx

Approved Uses

Cabometyx is used to treat several specific types of cancer that have reached an advanced stage or have spread to other parts of the body. It is typically prescribed for the following conditions:

• Renal Cell Carcinoma: This is a type of kidney cancer. Cabometyx may be used alone or in combination with nivolumab as a first treatment for advanced kidney cancer. It is also used alone for patients who have already received other treatments.
• Hepatocellular Carcinoma: This is a type of liver cancer. It is used for patients who have previously been treated with the medication sorafenib.
• Differentiated Thyroid Cancer: It is used for adults and children 12 years of age and older whose cancer has spread and no longer responds to treatment with radioactive iodine.
• Neuroendocrine Tumors: It is used for adults and children 12 years of age and older with advanced pancreatic neuroendocrine tumors (pNET) or extra-pancreatic neuroendocrine tumors (epNET) that have worsened after previous treatments.

Mechanism of Action

Cabometyx belongs to a class of medications called tyrosine kinase inhibitors (TKIs). It works by targeting and blocking the activity of specific proteins, or enzymes, that are found on the surface of cells. These proteins are often more active in cancer cells than in healthy cells.

This medication helps manage cancer through several different processes:

• Slowing tumor growth: It blocks signals that tell cancer cells to multiply and divide. By interfering with these growth signals, the drug can help shrink tumors or prevent them from growing larger.
• Cutting off blood supply: It inhibits a process called angiogenesis, which is the formation of new blood vessels. Tumors need their own blood supply to receive the oxygen and nutrients required to grow. By blocking this process, the medication can effectively starve the tumor.
• Reducing cancer spread: It targets specific pathways involved in metastasis, which is the process of cancer cells breaking away from the original tumor and spreading to other parts of the body.

Because Cabometyx targets specific proteins rather than all rapidly dividing cells, it is considered a targeted therapy. However, because these proteins are also present in some healthy tissues, the medication can affect non-cancerous cells in the body as well.

Common Side Effects

• Diarrhea
• Feeling very tired or weak
• Nausea and vomiting
• Decreased appetite and weight loss
• High blood pressure
• Hand-foot syndrome (redness, pain, or swelling on the palms of the hands or soles of the feet)
• Constipation
• Stomach-area pain
• Changes in the way food tastes
• Changes in hair color

Serious Side Effects

Some side effects can be severe and require immediate medical attention. These may include:

• Severe bleeding, such as coughing up blood, bloody stools, or unusual bruising
• Tears (perforations) or abnormal openings (fistulas) in the stomach or intestines
• Blood clots, which can lead to a heart attack, stroke, or lung problems
• Severe high blood pressure or hypertensive crisis
• Jaw bone problems (osteonecrosis), which may cause jaw pain or sores in the mouth
• Wound healing complications
• Liver problems, which may cause yellowing of the skin or eyes
• Reversible posterior leukoencephalopathy syndrome (RPLS), a brain condition that can cause seizures, headaches, or vision changes

Serious Bleeding and Gastrointestinal Issues

Cabometyx can cause severe or fatal bleeding (hemorrhage). It also increases the risk of developing perforations (holes) or fistulas (abnormal connections) in the stomach or intestines. Symptoms such as severe abdominal pain, black or bloody stools, or coughing up blood require immediate medical evaluation.

Cardiovascular and Blood Pressure Risks

High blood pressure is common and can become severe. Blood pressure is typically monitored regularly, and treatment may be adjusted or paused if it cannot be controlled. There is also an increased risk of blood clots, heart attack, and stroke.

Wound Healing and Surgery

This medication can interfere with the body's ability to heal wounds. It is generally recommended to stop taking the drug at least three weeks before a scheduled surgery or dental procedure. Treatment is usually not restarted until the wound has healed sufficiently.

Liver and Kidney Function

When used in combination with certain other medications, such as nivolumab, there is an increased risk of liver toxicity. Regular blood tests are used to monitor liver enzymes. Additionally, the drug may cause protein to leak into the urine (proteinuria), which can indicate kidney stress.

Other Serious Precautions

• Hand-Foot Syndrome: Redness, pain, or swelling on the palms of the hands or soles of the feet may occur and may require dose adjustments.
• Osteonecrosis of the Jaw: This is a serious condition where the jawbone is damaged. It is often associated with invasive dental procedures.
• Reversible Posterior Leukoencephalopathy Syndrome (RPLS): A rare brain condition characterized by seizures, headache, confusion, or vision changes.
• Pregnancy Risk: This medication can cause fetal harm. Effective birth control is necessary during treatment and for at least four months after the final dose.

Pregnancy

Cabometyx may cause fetal harm if taken during pregnancy. Healthcare providers typically perform a pregnancy test before a patient starts this medication to ensure they are not pregnant. Individuals who can become pregnant should use effective birth control during treatment and for at least 4 months after the final dose.

Breastfeeding

It is not known if this medication passes into breast milk. Because of the potential for serious adverse reactions in a nursing infant, breastfeeding is not recommended during treatment and for at least 4 months after the last dose.

Fertility

This medication may affect fertility in both men and women, which could impact the ability to have children in the future. Patients should discuss any concerns regarding fertility or family planning with their healthcare provider before starting treatment.

Dosage Forms

Cabometyx is available in the following form:

• Oral Tablet: A film-coated tablet designed to be swallowed whole.

It is important to use only the specific form prescribed by a healthcare provider. Cabometyx tablets and cabozantinib capsules are not interchangeable and cannot be substituted for one another.

FDA Approval History

Cabometyx (cabozantinib) was first approved by the U.S. Food and Drug Administration (FDA) in April 2016. Since its initial approval, the FDA has expanded its use to include several different types of advanced or metastatic cancers.

Approved Indications

The FDA has approved Cabometyx for the following conditions:

• Renal Cell Carcinoma (RCC): For the treatment of patients with advanced kidney cancer.
• Hepatocellular Carcinoma (HCC): For patients with liver cancer who have previously been treated with the drug sorafenib.
• Differentiated Thyroid Cancer (DTC): For patients 12 years of age and older with radioactive iodine-refractory disease that has progressed after prior therapy.
• Neuroendocrine Tumors (NET): For adult and pediatric patients 12 years and older with advanced or metastatic pancreatic neuroendocrine tumors (pNET) or extra-pancreatic neuroendocrine tumors (epNET).

Safety and Regulatory Status

Cabometyx does not currently have a Boxed Warning, which is the FDA’s most serious type of warning. However, the medication is associated with significant safety risks, including severe high blood pressure, gastrointestinal perforations, and serious bleeding. It is available only by prescription and must be administered under the supervision of a healthcare provider experienced in using anticancer therapies.

Insurance and Prior Authorization

Cabometyx is classified as a specialty medication. Because of its high cost and specific use, most insurance providers, including Medicare and Medicaid, require a process called prior authorization. During this process, a healthcare provider must submit documentation to the insurance company to prove the medication is medically necessary before coverage is approved.

Specialty Pharmacy Distribution

Unlike common medications, Cabometyx is typically not available at local retail pharmacies. It is usually dispensed through specialty pharmacies. these pharmacies are equipped to handle high-cost oncology drugs and often provide additional support, such as coordinating delivery and assisting with insurance claims.

Financial Assistance Programs

Several options may be available to help reduce out-of-pocket expenses for patients:

• Copay Savings Cards: Patients with commercial or private insurance may be eligible for manufacturer-sponsored programs that can significantly lower monthly copayments.
• Patient Assistance Programs: For individuals who are uninsured or meet specific financial criteria, the manufacturer or independent charitable foundations may provide the medication at a reduced cost or for free.
• Foundation Grants: Some non-profit organizations offer grants to help patients cover the coinsurance or copayments associated with cancer treatments.