Kadcyla

Approved Uses

Kadcyla is used to treat HER2-positive breast cancer in two primary situations:

• Early Breast Cancer: It is used as an additional treatment (adjuvant therapy) for patients who have already received chemotherapy and trastuzumab before surgery, but still have cancer cells remaining in the breast or lymph nodes at the time of surgery.
• Metastatic Breast Cancer: It is used for patients whose cancer has spread to other parts of the body (metastatic) and who have previously received treatment with trastuzumab and a taxane chemotherapy drug.

Before starting Kadcyla, a healthcare provider will perform a test to confirm that the cancer is HER2-positive, as the medication is only effective for this specific type of tumor.

Targeted Delivery

Kadcyla is an antibody-drug conjugate, which means it acts as a delivery system for chemotherapy. It is made of two main components: an antibody called trastuzumab and a chemotherapy drug called emtansine (DM1). These components are joined by a linker that keeps them together until they reach their target.

Mechanism of Action

The medication works through the following steps to identify and destroy specific cancer cells:

• Identification: The antibody portion of Kadcyla is designed to seek out and attach to HER2 receptors, which are proteins found in large amounts on the surface of certain cancer cells.
• Internalization: After Kadcyla attaches to the HER2 receptor, the cancer cell absorbs the entire drug.
• Activation: Once inside the cell, the chemotherapy (emtansine) is released. It works by disrupting the cell's microtubules, which are structures necessary for the cell to divide and grow.
• Cell Death: By preventing cell division, the chemotherapy causes the cancer cell to die.

In addition to delivering chemotherapy, the trastuzumab portion of the drug may also help the body's immune system identify and attack the cancer cells while blocking signals that tell the cancer to grow. By targeting cells with high levels of HER2, Kadcyla is designed to limit the amount of chemotherapy that reaches healthy cells.

Common Side Effects

Many people receiving Kadcyla experience mild to moderate side effects. These may include:

• Fatigue or feeling weak
• Nausea and vomiting
• Pain in the muscles, bones, or joints
• Headache
• Constipation or diarrhea
• Cough
• Numbness, tingling, or burning pain in the hands or feet
• Trouble sleeping
• Dry mouth

Serious Side Effects

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

• Liver problems: Symptoms may include yellowing of the skin or eyes (jaundice), dark urine, or pain in the upper right stomach area.
• Heart problems: This medication can affect how well the heart pumps blood, which may lead to shortness of breath, swelling in the legs or ankles, or a sudden cough.
• Lung problems: Inflammation of the lungs (pneumonitis) can cause trouble breathing, chest pain, or a new or worsening cough.
• Low platelet counts: A decrease in platelets can increase the risk of easy bruising or serious bleeding.
• Infusion reactions: Some people experience reactions during or shortly after the injection, such as fever, chills, or dizziness.
• Nerve damage: Persistent or worsening numbness and tingling in the extremities, known as peripheral neuropathy.

Boxed Warnings

Kadcyla has several boxed warnings regarding serious risks that require close medical supervision:

• Hepatotoxicity: Severe liver damage, including liver failure and death, has occurred in patients treated with this medication. A specific condition called nodular regenerative hyperplasia (NRH) of the liver has also been reported. Liver function is typically monitored before each dose.
• Cardiac Toxicity: This medication may cause a decrease in left ventricular ejection fraction (LVEF), which can lead to heart failure. Heart function is usually evaluated before starting treatment and at regular intervals during therapy.
• Embryo-Fetal Toxicity: Exposure to Kadcyla during pregnancy can cause birth defects or fetal death. Effective contraception is required for patients of reproductive potential during treatment and for a specific period after the final dose.

Medication Errors

There is a significant risk of confusion between Kadcyla (ado-trastuzumab emtansine) and Herceptin (trastuzumab). These drugs are different and are not interchangeable. Using the wrong medication can lead to dosing errors and serious adverse reactions.

Other Serious Risks

Additional precautions and potential complications include:

• Pulmonary Toxicity: Serious lung conditions, such as interstitial lung disease or pneumonitis, have been reported. Treatment may need to be permanently discontinued if severe respiratory symptoms develop.
• Hemorrhage: Serious and sometimes fatal bleeding events have occurred. The risk may be higher for patients also taking antiplatelet or anticoagulant medications, or those with low platelet counts.
• Thrombocytopenia: A decrease in blood platelets (thrombocytopenia) is common and can increase the risk of bleeding. Platelet counts are typically monitored prior to each dose.
• Neurotoxicity: Peripheral neuropathy, characterized by numbness, tingling, or pain in the hands and feet, may occur or worsen during treatment.
• Infusion-Related Reactions: Some patients may experience reactions during or shortly after the infusion, such as fever, chills, flushing, or trouble breathing. Infusions may be slowed or interrupted if these symptoms occur.

Pregnancy

Kadcyla can cause fetal harm or death when administered to a pregnant woman. Clinical data indicates that exposure to this medication during pregnancy can lead to oligohydramnios, a condition where there is too little amniotic fluid. This can result in life-threatening complications for the fetus, including underdeveloped lungs and skeletal deformities.

Healthcare providers typically perform a pregnancy test before starting Kadcyla to ensure the patient is not pregnant. Patients of reproductive potential are advised to use effective contraception during treatment and for 7 months after the last dose. If pregnancy occurs during treatment, it is important to notify a doctor immediately.

Breastfeeding

There is no information on whether Kadcyla is present in human breast milk or its effects on a breastfed infant. Because of the potential for serious adverse reactions, breastfeeding is not recommended during treatment and for 7 months after the final dose. Patients should consult with their healthcare provider to determine the best way to feed their baby during this time.

Available Forms

Kadcyla is supplied as a sterile, preservative-free lyophilized powder in single-dose vials.

This medication is administered as an intravenous infusion. Before use, the powder must be reconstituted and then diluted by a healthcare professional. It is not designed for other routes of administration, such as an intravenous push or bolus.

It is important to note that Kadcyla (ado-trastuzumab emtansine) is a different medication than trastuzumab and they are not interchangeable.

FDA Approval History

The U.S. Food and Drug Administration (FDA) first approved Kadcyla in February 2013. It was initially indicated for patients with HER2-positive metastatic breast cancer who had previously received trastuzumab and a taxane chemotherapy. In May 2019, the FDA expanded the approval to include the adjuvant (after surgery) treatment of patients with HER2-positive early breast cancer who have residual invasive disease after receiving neoadjuvant (before surgery) treatment.

Boxed Warnings

Kadcyla carries Boxed Warnings, the FDA's most serious type of warning, for the following risks:

• Hepatotoxicity: Serious liver injury, including liver failure and death, has occurred in patients treated with this medication. Liver function should be monitored prior to each dose.
• Cardiac Toxicity: Treatment may lead to a reduction in left ventricular ejection fraction (LVEF), which can cause heart failure.
• Embryo-Fetal Toxicity: Exposure to Kadcyla during pregnancy can cause birth defects or fetal death. Patients of reproductive potential should use effective contraception during treatment.

Safety Communications and Medication Errors

The FDA has issued safety communications regarding potential medication errors due to confusion between Kadcyla (ado-trastuzumab emtansine) and Herceptin (trastuzumab). These two drugs have different dosing schedules and are not interchangeable. The FDA has also monitored reports of interstitial lung disease and pneumonitis through the FDA Adverse Event Reporting System (FAERS) to identify potential new safety information.

Factors Influencing Cost

The total price of Kadcyla treatment can vary significantly based on several factors. Because it is a specialty biologic medication administered by a healthcare professional, the cost is generally higher than standard prescription drugs.

• Weight-Based Dosing: Kadcyla is administered based on a patient's body weight. Larger doses require more medication, which increases the cost per session.
• Administration Fees: Since the drug is given as an intravenous infusion, the total cost includes the price of the drug as well as fees for the clinic or hospital, nursing staff, and supplies.
• Insurance Coverage: Most insurance plans cover Kadcyla, but out-of-pocket expenses like deductibles and coinsurance will vary. Many insurers require prior authorization before treatment begins.

Financial Support Options

Patients may have access to financial assistance programs to help manage the cost of Kadcyla. These often include:

• Copay Cards: The manufacturer may offer programs to help commercially insured patients with their out-of-pocket costs.
• Patient Assistance Programs: For those without insurance or who are underinsured, non-profit organizations or the manufacturer may provide the medication at a reduced cost or for free based on financial need.

Currently, there are no lower-cost biosimilar versions of Kadcyla available on the market.