Pertuzumab

Approved Uses

Pertuzumab is used to treat a specific type of breast cancer known as HER2-positive breast cancer. This type of cancer involves cells that have high levels of the HER2 protein, which promotes cell growth. It is used in several different stages of treatment:

• Metastatic Breast Cancer: For cancer that has spread to other parts of the body, pertuzumab is used in combination with other medications (trastuzumab and docetaxel) for patients who have not yet received treatment for their metastatic disease.
• Early-Stage Breast Cancer (Before Surgery): Also known as neoadjuvant therapy, it is used before surgery to help treat early-stage, locally advanced, or inflammatory breast cancer.
• Early-Stage Breast Cancer (After Surgery): Also known as adjuvant therapy, it is used after surgery for patients who have a high risk of their cancer coming back.

Pertuzumab is always used as part of a combination treatment plan that includes other anti-cancer medications.

Targeting HER2 Proteins

Pertuzumab is designed to treat cancers that are HER2-positive. This means the cancer cells have an abnormally high amount of a protein called human epidermal growth factor receptor 2 (HER2) on their surface. These proteins send signals that tell the cancer cells to grow and divide rapidly.

Blocking Growth Signals

Pertuzumab works by attaching itself to a specific part of the HER2 protein. Once attached, it performs the following actions:

• Prevents Pairing: It blocks the HER2 protein from pairing up (dimerizing) with other members of the HER receptor family. This pairing is a necessary step for the protein to send growth signals into the cell.
• Interrupting Pathways: By preventing these pairs from forming, the drug interrupts the chemical pathways that lead to cell proliferation and survival.
• Immune System Activation: The medication may also help the body's immune system recognize the cancer cells as a threat, leading to the destruction of those cells.

Because it targets a specific protein found mostly on cancer cells, it is considered a targeted therapy rather than a traditional chemotherapy, though it is often used in combination with chemotherapy drugs.

Common Side Effects

Many people treated with pertuzumab experience side effects, which are often manageable. Common symptoms include:

• Diarrhea
• Hair loss
• Nausea and vomiting
• Fatigue or unusual weakness
• Skin rash
• Numbness, tingling, or burning pain in the hands or feet
• Low white blood cell counts, which may increase the risk of infection
• Mouth sores
• Muscle or joint pain
• Headache
• Changes in the sense of taste

Serious Side Effects

Some side effects require immediate medical attention. Contact a healthcare provider right away if you notice:

• Heart issues: Shortness of breath, swelling in the ankles or legs, palpitations, or a persistent cough.
• Infusion or injection reactions: Fever, chills, dizziness, or skin irritation at the administration site.
• Severe diarrhea: Intense or frequent bowel movements that may cause dehydration.
• Allergic reactions: Swelling of the face or throat, hives, and difficulty breathing.
• Lung inflammation: New or worsening breathing difficulties or cough.

Heart Problems

Pertuzumab can cause a decrease in the heart's ability to pump blood, which may lead to heart failure. This risk is increased when the drug is used in combination with other chemotherapy medications. Healthcare providers typically perform heart function tests, such as an echocardiogram or MUGA scan, before starting treatment and every few months during therapy.

Pregnancy and Fetal Harm

This medication can cause fetal harm or death when administered to a pregnant person. It is associated with low levels of amniotic fluid (oligohydramnios), which can lead to lung problems and skeletal defects in the fetus. A pregnancy test is required before starting treatment, and effective birth control must be used during therapy and for seven months after the final dose.

Infusion and Hypersensitivity Reactions

Severe allergic reactions, including anaphylaxis, have occurred. Patients are monitored closely during and after the infusion for signs of a reaction, such as:

• Fever or chills
• Nausea or vomiting
• Fatigue
• Headache

If a significant reaction occurs, the infusion may be slowed or stopped.

Low White Blood Cell Counts

When used with other chemotherapy drugs, pertuzumab may increase the risk of severe neutropenia (low white blood cell count). This condition can increase the risk of developing serious infections and may require monitoring of blood counts.

Pregnancy

Pertuzumab can cause serious harm, including birth defects or the death of an unborn baby, if administered during pregnancy. It has been linked to a condition called oligohydramnios, which is a significant decrease in the fluid surrounding the baby in the womb. This lack of fluid can lead to poor lung development and skeletal abnormalities in the fetus.

Before starting treatment, healthcare providers typically require a pregnancy test to ensure you are not pregnant. If you are able to become pregnant, you must use effective birth control during treatment and for at least 7 months after your last dose. If you become pregnant while receiving pertuzumab, you should notify your healthcare provider immediately.

Breastfeeding

It is not known whether pertuzumab passes into human breast milk. Because many drugs are excreted in milk and there is a potential for serious side effects in a nursing infant, a decision should be made whether to discontinue breastfeeding or discontinue the medication. You should discuss the risks and benefits with your healthcare provider to determine the safest approach for you and your baby.

Available Forms

Pertuzumab is provided as a liquid solution for administration by a healthcare professional. It is available in the following formats:

• Intravenous Infusion: This form is a concentrated solution supplied in single-dose vials. A healthcare provider must dilute the solution before it is administered into a vein.
• Subcutaneous Injection: Pertuzumab is also available as part of a combination product that is administered as an injection under the skin.

FDA Approval and Indications

Pertuzumab is approved by the U.S. Food and Drug Administration (FDA) for use in combination with other therapies to treat HER2-positive breast cancer. Its approved indications include:

• Metastatic Breast Cancer: Used in combination with trastuzumab and docetaxel for patients who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.
• Neoadjuvant Treatment: Used before surgery for patients with HER2-positive, locally advanced, inflammatory, or early-stage breast cancer.
• Adjuvant Treatment: Used after surgery for patients with HER2-positive early breast cancer at high risk of recurrence.

Boxed Warnings

The FDA has issued Boxed Warnings for pertuzumab regarding the following risks:

• Cardiomyopathy: Pertuzumab can cause a decrease in left ventricular ejection fraction (LVEF), potentially leading to heart failure. Heart function is monitored before starting treatment and at regular intervals during therapy.
• Embryo-Fetal Toxicity: Exposure to the drug during pregnancy can result in low amniotic fluid, delayed fetal kidney development, and fetal death. Patients must use effective contraception during treatment and for 7 months after the last dose.

Biosimilar Status

In 2024, the FDA approved the first interchangeable biosimilar for pertuzumab. This designation means the biosimilar meets additional regulatory standards that may allow it to be substituted for the reference product by a pharmacist, depending on state laws.

Factors Affecting Cost

Pertuzumab is a specialty medication administered as an intravenous (IV) infusion by healthcare professionals. Because it is not a medication you fill at a retail pharmacy, several factors contribute to the total expense:

• Administration Fees: Costs include the professional services of healthcare providers and the use of the infusion facility or hospital.
• Dosage and Frequency: The total cost depends on the weight-based dose and the number of treatment cycles required for a patient's specific condition.
• Combination Therapy: Pertuzumab is typically used in combination with other medications, such as trastuzumab and chemotherapy drugs, which increases the overall cost of the treatment plan.

Insurance and Financial Assistance

Most insurance plans, including Medicare Part B, generally cover pertuzumab when it is determined to be medically necessary. Coverage often requires prior authorization from the insurance provider before treatment begins. Patients may still be responsible for out-of-pocket costs such as deductibles, co-pays, or coinsurance.

Financial assistance programs may be available for eligible patients. These can include manufacturer-sponsored programs or assistance from non-profit organizations intended to help with the costs of specialty oncology medications.