pertuzumab (Rx)

Brand and Other Names:Perjeta
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

injectable solution

  • 30mg/mL (420mg/14 mL)

Early Breast Cancer

Neoadjuvant treatment

  • Indicated in combination with trastuzumab and docetaxel for the 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
  • Initial dose: 840 mg IV infusion over 60 min, THEN 420 mg IV infusion over 30-60 min q3Weeks
  • Trastuzumab: 8 mg/kg IV infusion over 90 min initially, then 6 mg/kg IV infusion over 30-90 min q3Weeks
  • Docetaxel: 75 mg/m² IV infusion initially; may increase to 100 mg/m² IV infusion q3Weeks if initial dose is well tolerated
  • Administer sequentially; pertuzumab and trastuzumab can be given in any order; docetaxel should be administered after pertuzumab and trastuzumab
  • Neoadjuvant dosage regimens
    • Administered q3Weeks for 3-6 cycles as part of 1 of the following treatment regimens for early breast cancer
    • 4 preoperative cycles of pertuzumab in combination with trastuzumab and docetaxel followed by 3 postoperative cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) as given in the NeoSphere trial
    • 3 or 4 preoperative cycles of FEC alone followed by 3 or 4 preoperative cycles of pertuzumab in combination with docetaxel and trastuzumab as given in TRYPHAENA and BERENICE trials 6 preoperative cycles of pertuzumab in combination with docetaxel, carboplatin, and trastuzumab (TCH) (escalation of docetaxel above 75 mg/m² is not recommended) as given in TRYPHAENA trial
    • 4 preoperative cycles of dose-dense doxorubicin and cyclophosphamide (ddAC) alone followed by 4 preoperative cycles of pertuzumab in combination with paclitaxel and trastuzumab as given in BERENICE trial
    • Following surgery, patients should continue to receive trastuzumab to complete 1 year of treatment (up to 18 cycles)
    • See also Administration
    • For detailed information on chemotherapy regimens, please refer to "Breast Cancer Treatment Protocols"

Adjuvant treatment

  • Indicated in combination with trastuzumab and chemotherapy for adjuvant treatment of patients with HER2-positive early breast cancer at high risk of recurrence
  • Initial dose: 840 mg IV infusion over 60 min, THEN 420 mg IV infusion over 30-60 min q3Weeks
  • Trastuzumab: 8 mg/kg IV infusion over 90 min initially, then 6 mg/kg IV infusion over 30-90 min q3Weeks
  • For a total of 1 year (up to 18 cycles) or until disease recurrence or unmanageable toxicity, whichever occurs first, as part of a complete regimen for early breast cancer, including standard anthracycline and/or taxane-based chemotherapy as given in APHINITY trial
  • Pertuzumab and trastuzumab should start on Day 1 of the first taxane-containing cycle
  • See also Administration

Metastatic Breast Cancer

Indicated in combination with trastuzumab and docetaxel for HER2-positive metastatic breast cancer in patients who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease

Initial dose: 840 mg IV infusion over 60 min, THEN 420 mg IV infusion over 30-60 min q3Weeks thereafter

Trastuzumab: 8 mg/kg IV infusion over 90 min initially, THEN 6 mg/kg IV infusion over 30-90 min q3Weeks thereafter

Docetaxel: 75 mg/m² IV infusion initially; may increase to 100 mg/m² IV infusion q3Weeks if initial dose is well tolerated

Dosage Modifications

Withhold or discontinue pertuzumab if trastuzumab is withheld or discontinued; may continue therapy with trastuzumab if docetaxel has been discontinued

Pertuzumab dose reductions are not recommended

Hepatic impairment: Safety and efficacy not established

Renal impairment

  • Mild-to-moderate (CrCl 30-90 mL/min): No dosage adjustment necessary
  • Severe (CrCl <30 mL/min): Safety and efficacy not established

Hypersensitivity

  • Discontinue immediately if severe hypersensitivity reaction occurs

Infusion-related reactions

  • Slow or interrupt infusion rate of if the patient develops an infusion-related reaction

Left ventricular ejection fraction (LVEF)

  • Monitor LVEF ~q12Weeks
  • For patients receiving anthracycline-based chemotherapy, a LVEF of ≥50% is required after completion of anthracyclines, before starting pertuzumab and trastuzumab
  • Withhold pertuzumab and trastuzumab for at least 3 weeks
    • Early breast cancer: LVEF drops to <50% with with ≥10% decrease below pretreatment values
    • Metastatic breast cancer: LVEF drops to <40% OR LVEF 40-45% with ≥10% decrease below pretreatment values
  • Resume pertuzumab and trastuzumab after 3 weeks
    • Early breast cancer: <10% below pretreatment values
    • Metastatic breast cancer: Resume therapy if LVEF >45% or 40-45% with <10% absolute decrease below baseline
    • If LVEF has worsened or not improved after 3 weeks, discontinue pertuzumab and trastuzumab, unless the benefits for the individual patient are deemed to outweigh the risks

Dosing Considerations

Patient selection

  • Patient selection should be based on HER2 protein overexpression or HER2 gene amplification in tumor specimen
  • Assessment of HER2 protein overexpression and HER2 gene amplification should be performed using FDA-approved tests specific for breast cancer by laboratories with demonstrated proficiency
  • Information on FDA-approved tests for the detection of HER2 protein overexpression and HER2 gene amplification is available at: http://www.fda.gov/CompanionDiagnostics

Gastric Cancer (Orphan)

Orphan designation for treatment of gastric cancer

Orphan sponsor

  • Genentech, Inc.; 1 DNA Way; South San Francisco, CA 94080-4990

Safety and efficacy not established

Based on a population pharmacokinetic analysis, no significant difference was observed in the pharmacokinetics of pertuzumab between patients <65 years and patients ≥65 years

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Adverse Effects

>10% (all grades,pertuzumab in combination with trastuzumab and docetaxel)

Alopecia (61%)

Diarrhea (67%)

Nausea (42%)

Neutropenia (53%)

Fatigue (37%)

Rash (34%)

Peripheral neuropathy (32%)

Decreased appetite (29%)

Mucosal inflammation (28%)

Asthenia (26%) Vomiting (24%)

Peripheral edema (23%)

Nail disorder (23%)

Myalgia (23%)

Anemia (23%)

Headache (21%)

Stomatitis (19%)

Pyrexia (19%)

Dysgeusia (18%)

Leukopenia (18%)

Upper respiratory tract infection (17%)

Constipation (15%) Arthralgia (15%)

Dyspnea (14%)

Febrile neutropenia (14%)

Increased lacrimation (14%)

Pruritus (14%)

Insomnia (13%)

Dizziness (13%)

Nasopharyngitis (12%)

Dry skin (11%)

>10% (Grade 3/4, pertuzumab in combination with trastuzumab and docetaxel)

Febrile neutropenia (13%)

Leukopenia (12%)

1-10% (Grade 3/4, pertuzumab in combination with trastuzumab and docetaxel)

Fatigue (2%)

Asthenia (2%)

Anemia (2%)

Mucosal inflammation (1%)

Pyrexia (1%)

Nail disorder (1%)

Nausea (1%)

Vomiting (1%)

Headache (1%)

<1% (Grade 3/4, pertuzumab in combination with trastuzumab and docetaxel)

Peripheral edema (0.5%)

Stomatitis (0.5%)

Postmarketing Reports

Thrombocytopenia

Infusion reactions

Tumor lysis syndrome (TLS)

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Warnings

Black Box Warnings

Left ventricular dysfunction (LVEF)

  • Subclinical and clinical cardiac failure manifesting as decreased LVEF and CHF may occur with pertuzumab therapy
  • Evaluate cardiac function prior to and during treatment
  • Discontinue treatment for a confirmed clinically significant decrease in left ventricular function

Embryo-fetal toxicity

  • Exposure to pertuzumab can result in embryo-fetal death and birth defects
  • Advise patients of these risks and the need for effective contraception
  • Also see Pregnancy

Contraindications

Hypersensitivity

Cautions

Decreases in LVEF have been reported with drugs that block HER2 activity; assess LVEF prior to initiation of pertuzumab and monitor regularly during treatment (see Dosage Modifications and Black Box Warnings)

Fetal harm may occur when pertuzumab is administered to a pregnant woman (see Pregnancy)

Infusion reactions has been associated with pertuzumab administration; observe patients closely for 60 minutes after the first infusion and for 30 minutes after subsequent pertuzumab infusions (see Dosing Modifications)

Severe hypersensitivity, including anaphylaxis, has been observed in clinical trials; monitor and treat appropriately if such reactions occur (see Contraindications and Dosage Modifications)

Cases of possible tumor lysis syndrome reported; patients with significant tumor burden (e.g., bulky metastases) may be at higher risk; patients could present with hyperuricemia, hyperphosphatemia, and acute renal failure which may represent possible TLS; providers should consider additional monitoring and/or treatment as clinically indicated

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Pregnancy & Lactation

Pregnancy

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to pertuzumab during pregnancy

Women who receive pertuzumab in combination with trastuzumab during pregnancy or within 7 months prior to conception are encouraged to enroll in the MotHER Pregnancy Registry by contacting 1-800-690-6720 or visiting http://www.motherpregnancyregistry.com/

Verify pregnancy status of females of reproductive potential prior to the initiation of pertuzumab

Advise pregnant women and females of reproductive potential that exposure to pertuzumab in combination with trastuzumab during pregnancy or within 7 months prior to conception can result in fetal harm, including embryo-fetal death or birth defects

Advise females of reproductive potential to use effective contraception during treatment and for 7 months following the last dose of pertuzumab in combination with trastuzumab

Lactation

Unknown whether distributed in breast milk; because of potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue breast feeding or discontinue the drug, taking into account the importance of the drug to the mother

This consideration should also take into account the elimination half-life of pertuzumab and the trastuzumab wash out period of 7 month

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

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Pharmacology

Mechanism of Action

Monoclonal antibody that binds to the extracellular dimerization domain of the human epidermal growth factor receptor 2 protein (HER2); mediates antibody-dependent cellular cytotoxicity by inhibiting proliferation of cells that overexpress HER2

Absorption

With an initial dose of 840 mg followed by a maintenance dose of 420 mg q3Weeks thereafter, steady-state concentration of pertuzumab was reached after first maintenance dose

Elimination

Half-life: 18 days

Total body clearance: 0.24 L/day

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Administration

IV Incompatibilities

Do not mix with other drugs

D5W

IV Compatibilities

0.9% NaCl

IV Preparation

Withdraw appropriate volume of pertuzumab from the vials

Dilute into a 250 mL of 0.9% NaCl PVC or non-PVC polyolefin infusion bag

Mix diluted solution by gentle inversion; do not shake

Administer immediately once prepared

If diluted infusion solution is not used immediately, it can be stored at 2-8°C for up to 24 hr

IV Administration

IV infusion only

Do not administer as an IV push or bolus

Loading dose: Infuse over 60 minutes Subsequent doses: Infuse over 30-60 minutes

Monitor for infusion related adverse effects (eg, hypersensitivity, pyrexia, chills, headache, fatigue, asthenia, vomiting) for 60 minutes following first infusion, and for 30 minutes following subsequent infusions

Pertuzumab, trastuzumab, and docetaxel should be administered sequentially

Pertuzumab and trastuzumab can be given in any order

Delayed or missed dose

  • Time between 2 doses <6 weeks: Administer 420 mg
  • Time between 2 doses >6 weeks: Administer initial dose of 840 mg, then subsequent doses of 420 q3wk

Storage

Unopened vials

  • Refrigerate at 2-8°C (36-46°F) until time of use
  • Do not freeze; do not shake
  • Keep vial in the outer carton in order to protect from light

Diluted solutions

  • Refrigerate at 2-8°C for up to 24 hr
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Formulary

FormularyPatient Discounts

Adding plans allows you to compare formulary status to other drugs in the same class.

To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

Adding plans allows you to:

  • View the formulary and any restrictions for each plan.
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  • Compare formulary status to other drugs in the same class.
  • Access your plan list on any device – mobile or desktop.

The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL Quantity Limits
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.