Xgeva

Bone Complications in Cancer Patients

Xgeva is used to prevent serious bone-related problems, such as fractures, pressure on the spinal cord, or the need for radiation or surgery to the bone. It is prescribed for patients with:

• Bone metastases from solid tumors (cancers that have spread to the bone from other organs).
• Multiple myeloma (a type of cancer that affects plasma cells in the bone marrow).

Giant Cell Tumor of Bone

This medication is used to treat a specific type of bone tumor called giant cell tumor of bone. It is used in adults and in adolescents whose skeletons have finished developing. It is typically chosen when the tumor cannot be surgically removed or when surgery would likely cause significant physical impairment.

High Calcium Levels

Xgeva is also used to treat hypercalcemia of malignancy, which is a condition where cancer causes high levels of calcium in the blood. It is used for this purpose when the condition does not respond to treatment with bisphosphonate drugs.

Targeting Bone-Removing Cells

Xgeva contains the active ingredient denosumab, which is a type of medicine called a monoclonal antibody. It is designed to target and bind to a protein in the body known as RANK ligand.

In a healthy body, bone is constantly being broken down and rebuilt. However, certain types of cancer can cause the body to produce too much RANK ligand. This protein signals specialized cells called osteoclasts to break down bone at an abnormally fast rate.

How Xgeva Helps

By binding to RANK ligand, Xgeva prevents it from activating the osteoclasts. This process helps in several ways:

• Strengthening Bone: It slows down the destruction of bone tissue, which helps prevent fractures and other bone problems caused by cancer that has spread to the bones.
• Controlling Tumor Growth: In cases of giant cell tumor of bone, it can help slow the growth of the tumor by targeting the cells that make up the mass.
• Lowering Calcium Levels: When bone is broken down too quickly, it releases calcium into the bloodstream. By stopping this breakdown, Xgeva helps lower dangerously high calcium levels caused by cancer.

Common Side Effects

Many people using Xgeva experience mild to moderate side effects. These may include:

• Tiredness or weakness
• Nausea or diarrhea
• Shortness of breath
• Headache
• Cough
• Pain in the joints, back, or muscles
• Low levels of phosphate in the blood

Serious Side Effects

While less common, some side effects can be severe and require immediate medical attention. Contact a healthcare provider if you experience:

• Low blood calcium (hypocalcemia): Symptoms include muscle spasms, twitches, cramps, or numbness and tingling in the fingers, toes, or around the mouth.
• Jaw bone problems (osteonecrosis): Symptoms include jaw pain, swelling, numbness, or loose teeth. This risk may be higher after dental procedures or with poor oral hygiene.
• Unusual thigh bone fractures: New or unusual pain in the hip, groin, or thigh.
• Serious infections: Signs of infection in the skin, ears, or urinary tract, such as fever, chills, or skin that is red, swollen, and hot to the touch.
• Skin reactions: Severe rashes, itching, or dry, scaly skin (dermatitis or eczema).
• Severe allergic reactions: Swelling of the face, lips, or tongue, or difficulty breathing.

Hypocalcemia

Severe, life-threatening hypocalcemia (low blood calcium) can occur during treatment. Any pre-existing low calcium levels must be corrected before starting this medication. Healthcare providers typically monitor calcium, magnesium, and phosphorus levels, especially in patients with severe kidney impairment or those receiving dialysis. Supplementation with calcium and vitamin D is often necessary unless high blood calcium is present.

Osteonecrosis of the Jaw (ONJ)

This medication is associated with a risk of osteonecrosis of the jaw, a condition where the jawbone is exposed and fails to heal. Risk factors include poor oral hygiene, invasive dental procedures such as tooth extractions, and certain concurrent treatments like chemotherapy or corticosteroids. A dental examination and preventive dentistry are recommended before starting treatment. While using this medication, maintaining good oral hygiene is important, and invasive dental procedures should be avoided if possible.

Atypical Femoral Fractures

Atypical fractures of the thigh bone (femur) have been reported in patients. These fractures may occur with little or no trauma and can be preceded by several weeks or months of thigh or groin pain. Patients experiencing new or unusual pain in these areas should be evaluated to rule out an incomplete fracture.

Risks After Stopping Treatment

Discontinuing treatment can lead to serious complications in specific populations:

• Hypercalcemia: Clinically significant high blood calcium levels may occur after stopping treatment, particularly in patients with growing skeletons or those treated for giant cell tumor of bone. This may require hospitalization.
• Multiple Vertebral Fractures: There is an increased risk of multiple fractures in the spine after the medication is discontinued. If treatment is stopped, healthcare providers may transition the patient to a different bone-strengthening therapy.

Embryo-Fetal Toxicity

This medication can cause harm to an unborn baby. It is not recommended for use during pregnancy. Effective contraception should be used during treatment and for at least five months after the last dose.

Hypersensitivity

Serious allergic reactions, including anaphylaxis, have occurred. Symptoms may include low blood pressure, difficulty breathing, throat tightness, or swelling of the face, lips, or tongue. If a systemic allergic reaction occurs, the medication is typically discontinued permanently.

Pregnancy

Xgeva can cause harm to an unborn baby. Animal studies have shown that exposure to this medication during pregnancy may lead to an increased risk of fetal loss, stillbirth, and problems with bone and lymph node development. It is generally advised that this medication should not be used by pregnant women.

If you are a person of childbearing potential, your healthcare provider may require a pregnancy test before you start treatment to ensure you are not pregnant. You should use effective contraception while receiving Xgeva and for at least 5 months after your final dose.

If you become pregnant while taking this medication or within 5 months after your last dose, notify your healthcare provider immediately.

Breastfeeding

It is currently unknown whether Xgeva passes into human breast milk. Because of the potential for serious side effects in a nursing infant, healthcare providers typically recommend either stopping breastfeeding or stopping the medication. The decision depends on the importance of the treatment to the mother's health.

Available Forms

Xgeva is supplied as a sterile, preservative-free solution for subcutaneous injection. It is typically provided in a single-dose vial.

Strengths

This medication is available in a specific concentration for injection. The solution is clear and may range in color from colorless to pale yellow. It is intended for administration by a healthcare provider and should not be self-administered.

FDA Approval History

The U.S. Food and Drug Administration (FDA) first approved Xgeva in 2010. Its approved uses include the prevention of skeletal-related events in patients with multiple myeloma or bone metastases from solid tumors. It is also indicated for the treatment of giant cell tumor of bone in adults and skeletally mature adolescents, as well as hypercalcemia of malignancy that is refractory to bisphosphonates.

Boxed Warning

Xgeva includes a Boxed Warning for severe hypocalcemia in patients with advanced chronic kidney disease. Patients with severe renal impairment, especially those on dialysis, are at an increased risk of developing dangerously low blood calcium levels. Monitoring of calcium levels and supplementation with calcium and vitamin D are typically required during treatment.

Biosimilar Status

In March 2024, the FDA approved the first interchangeable biosimilars for Xgeva. These products are biological medications that have been shown to be highly similar to Xgeva with no clinically meaningful differences in safety or effectiveness.

Factors Influencing Cost

The total price you pay for Xgeva can be influenced by several variables:

• Insurance Coverage: Most private insurance plans and Medicare Part B typically cover Xgeva, but your out-of-pocket costs like copays or coinsurance will depend on your specific plan.
• Administration Fees: Because Xgeva is administered as a subcutaneous injection by a healthcare professional, you may be charged for the office visit and the procedure in addition to the medication itself.
• Treatment Setting: Costs may differ depending on whether you receive the injection at a doctor's office, an outpatient clinic, or a hospital facility.

Biosimilar Options

The FDA has approved interchangeable biosimilars for Xgeva, such as Wyost. A biosimilar is a biological product that is highly similar to and has no clinically meaningful differences from an existing FDA-approved reference product. Interchangeable biosimilars may be substituted for the brand-name drug at the pharmacy level, depending on state laws, which can help lower treatment expenses.

Financial Assistance Programs

Patients who are uninsured or underinsured may have access to financial assistance. The manufacturer often provides support programs or copay cards to help eligible patients reduce their out-of-pocket costs. Additionally, some non-profit organizations offer grants to help cover the cost of specialized medications for bone health and cancer-related conditions.