Usual Adult Dose for Breast Cancer

METASTATIC BREAST CANCER (MBC):
840 mg IV over 60 minutes, followed by 420 mg IV over 30 to 60 minutes every 3 weeks

NEOADJUVANT TREATMENT OF BREAST CANCER:
840 mg IV over 60 minutes, followed by 420 mg IV every 3 weeks over 30 to 60 minutes

• This drug should be administered every 3 weeks for 3 to 6 cycles as part of one of the following treatment regimens for early breast cancer:

1) Four preoperative cycles of this drug in combination with trastuzumab and docetaxel followed by 3 postoperative cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC).
2) Three or 4 preoperative cycles of FEC alone followed by 3 or 4 preoperative cycles of this drug in combination with docetaxel and trastuzumab.
3) Six preoperative cycles of this drug in combination with docetaxel, carboplatin, and trastuzumab (TCH).
4) Four preoperative cycles of dose-dense doxorubicin and cyclophosphamide (ddAC) alone followed by 4 preoperative cycles of this drug in combination with paclitaxel and trastuzumab.

• Following surgery, patients should continue to receive this drug and trastuzumab for one 1 year (up to 18 cycles) or until disease recurrence or unmanageable toxicity, as part of a complete regimen for early breast cancer, including standard anthracycline- and/or taxane-based chemotherapy.

Comments:

• Consult the manufacturer product information or local protocol for dosing of concomitant medications and recommended schedules of administration.
• Select patients based on HER2 protein overexpression or HER2 gene amplification in tumor specimens. Assessment of HER2 protein overexpression and HER2 gene amplification should be performed using approved tests specific for breast cancer.
• An observation period of 30 to 60 minutes is recommended after each infusion and before any subsequent infusion.

Uses:
1) In combination with trastuzumab and docetaxel for treatment of patients with HER2-positive metastatic breast cancer (MBC) who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease
2) In combination with trastuzumab and chemotherapy as:

• Neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer -Adjuvant treatment of patients with HER2-positive early breast cancer at high risk of recurrence

Renal Dose Adjustments

Mild to moderate renal dysfunction: No adjustment recommended
Severe renal dysfunction: Data not available

Liver Dose Adjustments

Data not available

Dose Adjustments

• For delayed or missed doses, if the time between 2 sequential infusions is less than 6 weeks, the 420-mg dose of this drug should be administered. Do not wait until the next planned dose. If the time between 2 sequential infusions is 6 weeks or more, the initial dose of 840 mg of this drug should be readministered as a 60-minute IV infusion followed every 3 weeks thereafter by a dose of 420 mg administered as an IV infusion over 30 to 60 minutes.
• Discontinue this drug if trastuzumab therapy is discontinued.
• Dose reductions are not recommended for this drug.

DOSE MODIFICATIONS FOR LEFT VENTRICULAR EJECTION FRACTION (LVEF) DYSFUNCTION:
1) Metastatic Breast Cancer (MBC):

• Pretreatment LVEF level should be 50% or greater.
• Monitor LVEF about every 12 weeks.
• Withhold pertuzumab and trastuzumab dosing for at least 3 weeks for either: a drop in LVEF to less than 40% OR LVEF of 40% to 45% with a 10% or greater absolute decrease below pretreatment values.
• Resume pertuzumab and trastuzumab if the LVEF has recovered to greater than 45% or to 40% to 45% with a fall of less than a 10% points below pretreatment values.

2) Early Breast Cancer:

• Pretreatment LVEF level should be 55% or greater (for patients receiving anthracycline-based chemotherapy, a LVEF of 50% or greater is required after completion of anthracyclines, before starting this drug and trastuzumab).
• Monitor LVEF about every 12 weeks.
• Withhold pertuzumab and trastuzumab dosing for at least 3 weeks for either: a drop in LVEF to less than 40% OR LVEF of 40% to 45% with a 10% or greater absolute decrease below pretreatment values.
• Resume pertuzumab and trastuzumab if the LVEF has recovered to greater than 45% or to 40% to 45% with a fall of less than a 10% points below pretreatment values.

• Hypersensitivity Reactions/Anaphylaxis:
• The infusion rate may be slowed or interrupted if the patient develops an infusion-related reaction. Treatment including oxygen, beta agonists, antihistamines, rapid IV fluids, and antipyretics may also help alleviate symptoms.
• Discontinue the infusion immediately if the patient develops a serious infusion-related reaction.

Precautions

US BOXED WARNINGS:

• LEFT VENTRICULAR DYSFUNCTION: This drug can result in subclinical and clinical cardiac failure manifesting as CHF, and decreased left ventricular function (LVEF). Evaluate cardiac function prior to and during treatment. Discontinue this drug for a confirmed clinically significant decrease in LVEF.
• EMBRYOFETAL TOXICITY: Exposure to this drug can result in embryofetal death and birth defects. Studies in animals have resulted in oligohydramnios, delayed renal development, and death. Advise patients of these risks and the need for effective contraception.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• This drug should only be administered under supervision of a healthcare professional experienced in the treatment of cancer patients.
• Do not administer this drug as an IV push or bolus.
• Pertuzumab and trastuzumab may be administered in any order; however, when the patient is receiving docetaxel, the docetaxel dose should be given after both pertuzumab and trastuzumab infusions.
• In patients receiving an anthracycline-based regimen, pertuzumab and trastuzumab should be administered following completion of the anthracycline.
• Patients should be observed for 30 to 60 minutes after each pertuzumab infusion and before any subsequent infusions of trastuzumab or docetaxel.

Storage requirements:

• Vials should be stored in a refrigerator at 2C to 8C, kept in the outer carton to protect from light.
• Do not freeze or shake the vials.
• If storage is necessary upon dilution, the solution may be stored at 2C to 8C for up to 24 hours.

Reconstitution/preparation techniques:

• The manufacturer product information should be consulted.

IV compatibility:

• This drug is compatible with 0.9% sodium chloride.
• This drug is incompatible with 5% glucose solution and should not be mixed or diluted with other drugs.

General:

• This drug may only be used in patients with a HER2-positive tumor status, determined by a specialized laboratory.

Monitoring:

• Cardiovascular: LVEF
• Hematologic: Full blood count
• Hypersensitivity: Close observation of the patient for infusion-related reactions during and following infusions

Frequently asked questions

• How long can you stay on Herceptin and Perjeta?
• How do Herceptin (trastuzumab) and Perjeta (pertuzumab) work together?
• How much does Perjeta cost?
• Is Perjeta a chemotherapy drug?