Pertuzumab - Uses, Dosage, Side Effects, Drug Warnings, and Precautions

Introduction:

Pertuzumab is a chemotherapeutic agent. This drug belongs to the class of antineoplastic agents. It is a humanized monoclonal antibody that is derived from mice. It treats metastatic HER2-positive (human epidermal growth factor receptor 2) breast cancer. Pertuzumab is combined with Trastuzumab and Docetaxel and administered as an intravenous infusion to treat HER2-positive breast cancer.

Pertuzumab was developed by Genentech and was approved in 2012. The National Institute for Health and Care Excellence (NICE) in England evaluated Pertuzumab in 2015 and found that this drug could be more cost-effective. In May 2016, NICE rejected Pertuzumab for neoadjuvant breast cancer treatment, as it was unknown if the drug combination provides survival benefits. This decision was reversed in six months, and NICE approved Pertuzumab as a breast cancer drug as Roche pledged to provide Pertuzumab at an unclosed discount for the patients in NHS (National health care).

How Does Pertuzumab Work?

On activation, HER2, an extracellular receptor, causes signal transduction through various pathways and stimulates cell proliferation and growth. It causes uncontrollable cell growth if it is overexpressed. ERBB2 (erythroblastic oncogene B) gene amplification causes HER2-positive breast cancer. This gene amplification induces the overexpression of HER2 in 15 to 30 percent of breast cancers. HER2 or HER3 dimers activate the signaling pathway.

Pertuzumab binds to HER3, prevents the formation of HER2 or HER3 dimer, and blocks the signaling pathway, thereby preventing cell growth. Trastuzumab also binds to HER2 and prevents its function.

Uses

• Pertuzumab is combined with Trastuzumab and Docetaxel to treat HER2-positive metastatic breast cancer in patients who have not previously received anti-HER2 therapy or chemotherapy.

• It is combined with Trastuzumab and chemotherapy for neoadjuvant therapy (shrinks the cancer cells and prepares for other treatments like radiation therapy) in HER2-positive, locally advanced, inflammatory, or early-stage breast cancer.

• Pertuzumab is combined with Trastuzumab and chemotherapy for adjuvant therapy in HER2-positive early breast cancer at high risk for recurrence.

Dosage

HER2-Positive Metastatic Breast Cancer

Pertuzumab, Trastuzumab, and Docetaxel are administered as an intravenous infusion. Initially, 840 milligrams (mg) of Pertuzumab combined with Trastuzumab and Docetaxel are administered intravenously every three weeks in cycles. After that, 420 mg of Pertuzumab is administered intravenously in combination with Trastuzumab and Docetaxel.

Neoadjuvant Therapy for HER2-Positive Early Breast Cancer

Initially, 840 mg of Pertuzumab combined with Trastuzumab is administered intravenously, followed by 420 mg of Pertuzumab administered in combination with Trastuzumab every three weeks for three to six cycles. Pertuzumab and Trastuzumab are continued post-surgery to complete one year of therapy. Up to 18 cycles are required for treatment.

Adjuvant Therapy for HER2-Positive Early Breast Cancer

Initially, 840 mg of Pertuzumab combined with Trastuzumab is administered intravenously on the first day of the first taxane-containing cycle, followed by 420 mg of Pertuzumab combined with Trastuzumab every three weeks for one year up to 18 cycles or until the disease recurs.

What Are the Drug Warnings for Pertuzumab?

1) Left Ventricular Dysfunction: Pertuzumab decreases left ventricular function. It causes left ventricular systolic dysfunction. The patient's cardiac function should be evaluated before and during treatment with Pertuzumab. The drug should be discontinued if a decrease in left ventricular function occurs.

2) Pregnancy: Pertuzumab is embryotoxic and fetotoxic. It causes harm to the fetus and should not be used in pregnant women. A pregnancy test should be performed before starting this drug. Effective birth control methods should be used during therapy and seven months after discontinuation of this drug to prevent pregnancy.

3) Lactation: The distribution of Pertuzumab in breast milk is unknown. The risks and benefits should be weighed before starting Pertuzumab in breastfeeding mothers.

4) Infusion-Related Reactions: Patients should be monitored for infusion-related reactions like pyrexia, headache, fatigue, chills, vomiting, myalgia, and dysgeusia during infusion. The infusion rate should be reduced, or the drug should be permanently discontinued if such reactions are present.

5) Hypersensitivity Reactions: The drug should be discontinued if hypersensitivity reactions like swelling of the face and extremities, rashes, hives, and breathing difficulty occur.

6) HER2 Evaluation: Pertuzumab should be used in patients with HER2 gene amplification or HER2 gene overexpression. If HER2 is not present, the results may be unreliable.

For Patients

What Is a Chemotherapy Drug?

A chemotherapy drug refers to a medicine or a drug that is used in the treatment of cancer. Chemotherapy drugs are used in cancer treatment because they inhibit the growth of fast-growing cancer cells. These drugs have chemical substances that inhibit and prevent the growth of abnormal cells in the body. Various chemotherapeutic drugs are available, and each drug has a different mechanism of action. These drugs are used alone or in combination to treat various cancers. Pertuzumab is one drug used in combination to treat HER2-positive metastatic breast cancer.

What Does a Chemotherapy Drug Do?

Chemotherapy drugs are given as infusions, pills, shots, creams, or directly placed as wafers near the cancer site during or after surgery. It can be used as the primary treatment for cancer in some types of cancer. It can be used to kill the remaining cancer cells after surgery. It also shrinks the cells and prepares for other treatments like radiation therapy. In some cases, it is used as a palliative therapy in which the chemotherapy drug kills some cancer cells and offers relief from signs and symptoms.

What Is HER2-Positive Breast Cancer?

HER2-positive breast cancer is a type of breast cancer in which a protein called human epidermal growth factor receptor 2 (HER2) is present. HER2 promotes the growth of cancer cells. This type of breast cancer is more aggressive compared to other types of breast cancer. HER2-positive breast cancer is caused by the amplification of the ERBB2 (erythroblastic oncogene B) gene. This gene amplification induces the overexpression of HER2 in 15 to 30 percent of breast cancers. Overexpression of HER2 causes uncontrollable cell growth.

Things to Know Before Starting Pertuzumab:

When and Why Switch to Pertuzumab?

Various treatment strategies are followed in the treatment of HER2-positive breast cancer. Trastuzumab was the first drug approved for the treatment of HER2-positive breast cancer. However, resistance is common in Trastuzumab. Pertuzumab, combined with Trastuzumab and Docetaxel, effectively inhibits abnormal cell growth.

How Effective Is Pertuzumab?

Pertuzumab is a safe and effective drug in treating HER2-positive breast cancer. However, Pertuzumab or Trastuzumab alone is less effective in controlling cancer cell growth. Pertuzumab, in combination with Trastuzumab, is very effective in combating HER2-positive breast cancer cells. It improves the outcomes of patients with early breast cancer. It is also an effective neoadjuvant and adjuvant drug in treating HER2-positive breast cancer.

Things to Inform the Doctor Before Pertuzumab Is Prescribed

1. Pertuzumab should not be used if the patient is allergic to it.

2. It should not be given to pregnant women. Pregnancy or pregnancy planning should be discussed with the doctor.

3. The presence of heart disease, congestive heart failure, heart attack, uncontrolled hypertension, and cardiac rhythm disorder should be informed to the doctor.

4. The previous history of chemotherapy and radiotherapy, if present, should be informed to the doctor.

Starting Pertuzumab

How to Take Pertuzumab?

Pertuzumab is a chemotherapeutic drug administered into the vein by a doctor or healthcare professional. Pertuzumab is an injectable drug and is not available for oral use. Pertuzumab is usually given once every three weeks. It is usually used in combination and administered as an intravenous infusion. Initially, 840 mg is administered intravenously over 60 minutes, followed by 420 mg over 30 to 60 minutes every three weeks to treat HER2-positive metastatic breast cancer.

Do's and Don'ts While Under Pertuzumab:

1. It is important to visit the doctor regularly to check the progress and unwanted effects. Appointments should not be skipped.

2. Pertuzumab can harm the unborn baby. Therefore, effective birth control methods should be followed during and for seven months after completing the treatment. If pregnancy occurs during the treatment, they should be informed the doctor.

3. Pertuzumab can cause cardiac failure. Therefore, it should be informed if symptoms of heart failure like chest pain, breathing difficulty, and swelling of hands and feet occur.

4. It can cause infusion-related reactions like chills, dizziness, vomiting, breathing difficulty, headache, and chest pain. If such complaints are present, they should be informed.

5. It can cause allergic reactions like rashes, hives, breathing difficulties, and swelling of the face, hands, and feet. If such reactions are present, they should be informed to the doctor.

Advice for Caregivers

The caregivers should inform the doctor if the patient develops hypersensitivity reactions like rashes, hives, breathing difficulties, or other symptoms like chest pain or other abnormalities.

Things to Do After Taking Pertuzumab

It is essential to inform the doctor if any noticeable symptoms are present after taking Pertuzumab. Any signs of allergic reactions or symptoms like chest pain should be immediately informed to the doctor.

Diet Modifications

Diet modifications are not essential unless recommended by the doctor. A healthy and balanced diet can be followed during the treatment. However, the use of alcohol or tobacco is not recommended during the treatment.

Look Out for the Side Effects

The patients should familiarize themselves with Pertuzumab's common and rare side effects so that the symptoms can be easily recognized. If side effects are present, they should be informed to the doctor. Pertuzumab may cause some other side effects that are not listed here.

The common side effects include the following

• Burning, tingling, or painful sensations.

• Black stools.

• Chills.

• Cough.

• Rapid heartbeat.

• Fever.

• Itching or rashes.

• Lower back pain.

• Painful urination.

• Sore throat.

• Chest tightness.

• Redness of the skin.

• Ulcers or sores in the mouth.

• Breathing and swallowing difficulty.

• Unusual bleeding.

• Unusual tiredness.

• Loss of taste.

• Nasal congestion.

• Nausea.

• Vomiting.

Staying on Pertuzumab

Tips to Stay on Track:

Improvement in the symptoms of breast cancer can be experienced after taking Pertuzumab. If any side effects occur during treatment, it is essential to inform the doctor. Pertuzumab is given on a fixed schedule. Appointments should only be skipped by informing the doctor.

Things to remember,

1) It is important to stick to the dosage schedule of Pertuzumab because it will affect the treatment outcome if the dosage schedule is present.

2) It is essential to follow up regularly with the doctor and inform them about the improvement in the symptoms of breast cancer.

For Doctors

Indications:

Pertuzumab is indicated for use in HER2-positive metastatic breast cancer. It is combined with Trastuzumab and chemotherapy for neoadjuvant therapy in HER2-positive, locally advanced, inflammatory, or early-stage breast cancer. It is combined with Trastuzumab and used as adjuvant therapy in HER2-positive early breast cancer at high risk for recurrence.

Mechanism of Action:

ERBB2 gene amplification causes the overexpression of HER2 in 15 to 30 percent of breast cancers. HER2 or HER3 dimers activate the signaling pathway. On activation, HER2, an extracellular receptor, causes signal transduction through various pathways and stimulates cell proliferation and cell growth. It causes uncontrollable cell growth if it is overexpressed.

Pertuzumab binds to HER3, prevents the formation of HER2 or HER3 dimer, and blocks the signaling pathway, thereby preventing cell growth. Trastuzumab also binds to HER2 and prevents its function.

Pharmacodynamics:

Pertuzumab mediates antibody-dependent cell-mediated cytotoxicity. It inhibits the signaling pathways that cause abnormal cell growth. Pertuzumab alone can inhibit the proliferation of tumor cells. In combination with Trastuzumab, it induces anti-tumor activity against HER2 overexpression.

Absorption:

Intravenously administered 840 mg of Pertuzumab was followed by a maintenance dose of 420 mg every three weeks, which reached steady-state concentration after the first maintenance dose.

Distribution:

The average volume of distribution of Pertuzumab following intravenous administration is 3.53 to 7.5 liters.

Metabolism:

No information is available on the metabolism of Pertuzumab. However, monoclonal antibodies are subject to catabolism and are metabolized to smaller peptides and proteins before elimination.

Elimination:

The median half-life is 18 days, and the clearance rate of Pertuzumab is 0.24 liters per day.

Warnings and Precautions:

1) Pertuzumab decreases left ventricular function. It causes left ventricular systolic dysfunction. The patient's cardiac function should be evaluated before and during treatment with Pertuzumab. The drug should be discontinued if a decrease in left ventricular function occurs.

2) Pertuzumab is embryotoxic and fetotoxic. It causes harm to the fetus and should not be used in pregnant women. A pregnancy test should be performed before starting this drug. Effective birth control methods should be used during therapy and seven months after discontinuation of this drug to prevent pregnancy.

3) The distribution of Pertuzumab in breast milk is unknown. The risks and benefits should be weighed before starting Pertuzumab in breastfeeding mothers.

4) Patients should be monitored for infusion-related reactions like pyrexia, headache, fatigue, chills, vomiting, myalgia, and dysgeusia during infusion. The infusion rate should be reduced, or the drug should be permanently discontinued if such reactions are present.

5) The drug should be discontinued if hypersensitivity reactions like swelling of the face and extremities, rashes, hives, and breathing difficulty occurs.

6) Pertuzumab should be used in patients with HER2 gene amplification or HER2 gene overexpression. If HER2 is not present, the results may be unreliable.

Indications and Uses

• Pertuzumab is indicated for use in HER2-positive metastatic breast cancer. Pertuzumab is combined with Trastuzumab and Docetaxel to treat HER2-positive metastatic breast cancer in patients who have not previously received anti-HER2 therapy or chemotherapy.

• It is combined with Trastuzumab and chemotherapy for neoadjuvant therapy (shrinks the cancer cells and prepares for other treatments like radiation therapy) in HER2-positive, locally advanced, inflammatory, or early-stage breast cancer.

• Pertuzumab is combined with Trastuzumab and chemotherapy for adjuvant therapy in HER2-positive early breast cancer at high risk for recurrence.

Dosage Strength and Forms

Pertuzumab is an injectable drug available in 840 mg and 420 mg. Pertuzumab is usually given once every three weeks. It is usually used in combination and administered as an intravenous infusion. Initially, 840 mg is administered intravenously over 60 minutes, followed by 420 mg over 30 to 60 minutes every three weeks to treat HER2-positive metastatic breast cancer.

Considerations for Administration

• Pertuzumab should be given to patients with overexpression of HER2 overexpression.

• Patients should be closely observed for 60 minutes after infusion, as it may cause infusion-related reactions.

• Patients should be observed for hypersensitivity reactions after administration.

• Pertuzumab and Trastuzumab may be administered in any order.

Contraindications

1. Pertuzumab decreases left ventricular function. It causes left ventricular systolic dysfunction. Therefore, the patient's cardiac function should be evaluated before and during treatment with Pertuzumab. The drug should be discontinued if a decrease in left ventricular function occurs.

2. Pertuzumab harms the fetus and should not be used in pregnant women. A pregnancy test should be performed before starting this drug. Effective birth control methods should be used during therapy and seven months after discontinuation of this drug to prevent pregnancy.

3. The distribution of Pertuzumab in breast milk is not known. Therefore, the risks and benefits should be weighed before starting Pertuzumab in breastfeeding mothers.

4. Pertuzumab may cause hypersensitivity reactions. Therefore, it is contraindicated in patients who are allergic to Pertuzumab. The drug should be discontinued if hypersensitivity reactions like swelling of the face and extremities, rashes, hives, and breathing difficulty occur.

5. Pertuzumab should be used in patients with HER2 gene amplification or HER2 gene overexpression. If HER2 is not present, the results may be unreliable.

Results from Clinical Trials

A multicentered, double-blind, placebo-controlled trial called CLEOPATRA was performed on 808 patients with HER2-positive metastatic breast cancer. Patients were randomly administered placebo plus Trastuzumab and Docetaxel or Pertuzumab, Trastuzumab, and Docetaxel. Pertuzumab was initially administered intravenously at a dose of 840 mg, followed by 420 mg every three weeks. Docetaxel was given at a 75 mg per square meter dose by intravenous infusion every three weeks for at least six cycles. This study demonstrated a significant improvement in the Pertuzumab-treated group compared to the placebo group. Patients showed improvement in symptoms at the end of the analysis.

Drug Interactions

Interactions With Other Drugs

Pertuzumab should not be used with the following medications. If both medicines are prescribed, the doctor may change the dose or the period for one or both medicines.

It includes the following drugs:

• Daunorubicin.

• Daunorubicin Citrate Liposome.

• Daunorubicin Liposome.

• Doxorubicin.

• Epirubicin.

• Idarubicin.

• Pirarubicin.

• Pixantrone.

• Tofacitinib.

• Valrubicin.

Other Specifications

1) Left Ventricular Dysfunction: Pertuzumab decreases left ventricular function. It causes left ventricular systolic dysfunction. The patient's cardiac function should be evaluated before and during treatment with Pertuzumab. The drug should be discontinued if a decrease in left ventricular function occurs.

2) Pregnancy: Pertuzumab is embryotoxic and fetotoxic. It causes harm to the fetus and should not be used in pregnant women. A pregnancy test should be performed before starting this drug. Effective birth control methods should be used during therapy and seven months after discontinuation of this drug to prevent pregnancy.

3) Lactation: The distribution of Pertuzumab in breast milk is unknown. The risks and benefits should be weighed before starting Pertuzumab in breastfeeding mothers.

4) Infusion-Related Reactions: Patients should be monitored for infusion-related reactions like pyrexia, headache, fatigue, chills, vomiting, myalgia, and dysgeusia during infusion. The infusion rate should be reduced, or the drug should be permanently discontinued if such reactions are present.

5) Hypersensitivity Reactions: The drug should be discontinued if hypersensitivity reactions like swelling of the face and extremities, rashes, hives, and breathing difficulty occur.

6) Hepatic Impairment: Specific dosage modifications are not required for patients with hepatic impairment.

7) Renal Impairment: Dosage adjustment is not required for patients with mild or moderate renal impairment. No information is available on dose adjustments for patients with severe renal impairment.

8) Pediatric Use: The safety and efficacy of Pertuzumab in pediatric patients are not established.

9) Geriatric Use: There is no difference in safety and efficacy relative to young adult patients.