pertuzumab/trastuzumab/hyaluronidase

General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Genetic Implications:

Pronunciation:
per-tue-zue-mab/traz-too-zoo-mab/hye-al-yoor-on-i-dase

Trade Name(s)

Phesgo

Ther. Class.

antineoplastics

Pharm. Class.

HER2/neu receptor antagonists

monoclonal antibodies

Indications

Neoadjuvant treatment of human epidermal growth factor receptor 2 protein (HER2)-positive locally advanced, inflammatory, or early stage breast cancer (either >2 cm in diameter or node-positive) (in combination with chemotherapy).
Adjuvant treatment of HER2-positive early breast cancer at high risk of recurrence (in combination with chemotherapy).
HER2-positive metastatic breast cancer in patients who have not yet been treated with anti-HER2 agents or chemotherapy (in combination with docetaxel).

Action

Pertuzumab and trastuzumab: monoclonal antibody that binds to HER2 sites in breast cancer tissue and inhibits proliferation of cells that overexpress HER2 Hyaluronidase: Acts locally by depolymerizing hyaluronan, which increases permeability of the SUBQ tissue.

Therapeutic Effect(s):

Regression of breast cancer and metastases.

Pharmacokinetics

Pertuzumab

Absorption: 70% absorbed following SUBQ administration.

Distribution: Minimally distributed to tissues.

Metabolism and Excretion: Unknown.

Half-life: Unknown.

Trastuzumab

Absorption: 80% absorbed following SUBQ administration.

Distribution: Minimally distributed to tissues.

Metabolism and Excretion: Unknown.

Half-life: Unknown.

TIME/ACTION PROFILE (plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
Pertuzumab (SUBQ)	unknown	4 days	unknown
Trastuzumab (SUBQ)	unknown	4 days	unknown

Contraindication/Precautions

Contraindicated in:

Hypersensitivity;
OB: Pregnancy.

Use Cautiously in:

HF, uncontrolled hypertension, recent MI, arrhythmias, prior anthracycline exposure (equivalent to >360 mg/m² of doxorubicin);
Pulmonary disease or extensive tumor involvement of lungs (↑ risk of pulmonary toxicity);
Dyspnea at rest (↑ risk of hypersensitivity reaction);
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Rep: Women of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adverse Reactions/Side Effects

CV: arrhythmias, HF, hypertension, peripheral edema

Derm: alopecia, dry skin, rash, dermatitis, erythema, nail discoloration, palmar-plantar erythrodysesthesia syndrome

EENT: epistaxis, ↑ lacrimation, dry eyes, rhinorrhea

Endo: hypoglycemia

F and E: hyperkalemia, hyponatremia, hypernatremia, hypokalemia

GI: ↓ appetite, ↓ weight, ↑ liver enzymes, constipation, diarrhea, dyspepsia, hypoalbuminemia, nausea, stomatitis, vomiting, abdominal pain, hemorrhoids, hyperbilirubinemia

GU: ↑ serum creatinine, urinary tract infection

Hemat: anemia, leukopenia, lymphocytopenia, neutropenia, thrombocytopenia

Local: injection site pain, injection site reaction

MS: arthralgia, myalgia, muscle spasm, pain

Neuro: dizziness, dysgeusia, fatigue, headache, insomnia, paresthesia, peripheral neuropathy

Resp: cough, dyspnea, upper respiratory tract infection, ACUTE RESPIRATORY DISTRESS SYNDROME, INTERSTITIAL PNEUMONITIS, pleural effusion, PULMONARY EDEMA, PULMONARY FIBROSIS

Misc: fever, HYPERSENSITIVITY REACTIONS (including anaphylaxis and angioedema)

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

Use of an anthracycline (daunorubicin, doxorubicin, or idarubicin ) following therapy may ↑ risk of cardiotoxicity; if possible, avoid anthracycline-based therapy for up to 7 mo following completion of therapy.

Route/Dosage

Do not substitute Phesgo with or for pertuzumab, trastuzumab, ado-trastuzumab emtansine, or fam-trastuzumab deruxtecan.

Neoadjuvant Treatment of Breast Cancer

SUBQ (Adults): Initial dose: Pertuzumab 1,200 mg/trastuzumab 600 mg/hyaluronidase 10,000 units followed by maintenance dose in 3 wk; Maintenance dose: Pertuzumab 600 mg/trastuzumab 600 mg/hyaluronidase 20,000 units every 3 wk for 3–6 cycles as part of a treatment regimen for early breast cancer. Following surgery, continue pertuzumab/trastuzumab/hyaluronidase to complete 1 yr of treatment (up to 18 cycles) or until disease recurrence or unmanageable toxicity, whichever occurs first, as a part of a complete regimen for early breast cancer. In patients receiving an anthracycline-based regimen for early breast cancer, administer pertuzumab/trastuzumab/hyaluronidase following completion of the anthracycline. In patients receiving docetaxel or paclitaxel, administer docetaxel or paclitaxel after pertuzumab/trastuzumab/hyaluronidase.

Adjuvant Treatment of Breast Cancer

SUBQ (Adults): Initial dose: Pertuzumab 1,200 mg/trastuzumab 600 mg/hyaluronidase 10,000 units followed by maintenance dose in 3 wk; Maintenance dose: Pertuzumab 600 mg/trastuzumab 600 mg/hyaluronidase 20,000 units every 3 wk for a total of 1 yr (up to 18 cycles) or until disease recurrence or unmanageable toxicity, whichever occurs first, as part of a complete regimen for early breast cancer. In patients receiving an anthracycline-based regimen for early breast cancer, administer pertuzumab/trastuzumab/hyaluronidase following completion of the anthracycline. In patients receiving docetaxel or paclitaxel, administer docetaxel or paclitaxel after pertuzumab/trastuzumab/hyaluronidase.

Metastatic Breast Cancer

SUBQ (Adults): Initial dose: Pertuzumab 1,200 mg/trastuzumab 600 mg/hyaluronidase 10,000 units followed by maintenance dose in 3 wk; Maintenance dose: Pertuzumab 600 mg/trastuzumab 600 mg/hyaluronidase 20,000 units every 3 wk until disease recurrence or unmanageable toxicity. Administer docetaxel after pertuzumab/trastuzumab/hyaluronidase.

Availability

Solution for injection: pertuzumab 60 mg, trastuzumab 60 mg, and hyaluronidase 2,000 units/mL, pertuzumab 80 mg, trastuzumab 40 mg, and hyaluronidase 2,000 units/mL

Assessment

Conduct a cardiac assessment, including history, physical examination, and determination of left ventricular ejection fraction (LVEF) by echocardiogram or MUGA scan before starting therapy. Assess LVEF at regular intervals. May cause hypertension, arrhythmias, left ventricular dysfunction, HF, cardiomyopathy and death. For early breast cancer: with LVEF ≥55%, monitor LVEF every 12 wk. Hold Phesgo for at least 3 wk for LVEF ↓ to <50% with a fall of ≥10% points below pretreatment value. Resume Phesgo after 3 wk if LVEF recovered to ≥50% or <10% points below pretreatment value. For metastatic breast cancer with LVEF ≥50%, monitor LVEF every 12 wk. Hold Phesgo for 3 wk for LVEF ↓ to either <40% or 40–45% with a fall of ≥10% points below pre-treatment value. Resume Phesgo after 3 wk if LVEF has recovered to either >45% or 40–45% with a fall of <10% points below pretreatment value. After repeat assessment within 3 wk, if LVEF has not improved, has declined further, and/or patient is symptomatic, permanently discontinue Phesgo. After completion of therapy, continue to monitor for cardiomyopathy and assess LVEF measurements every 6 mo for at least 2 years.
Monitor for at least 30 min after initial dose of Phesgo and 15 min after each maintenance dose for signs of hypersensitivity symptoms or administration-related reactions. If significant injection-related reaction occurs, slow or pause injection and administer symptomatic therapy. Have medications and emergency equipment available. For Grade 1 or 2 hypersensitivity reactions, premedicate with an analgesic, antipyretic, or antihistamine. Permanently discontinue Phesgo if anaphylaxis or severe injection-related reactions.
Monitor for signs and symptoms of pulmonary toxicity (dyspnea, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, non-cardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, acute respiratory distress syndrome, pulmonary fibrosis) periodically during therapy.

Lab Test Considerations:

Patient selection is based on HER2 protein overexpression or HER2 gene amplification in tumor specimens using FDA-approved tests specific for breast cancer. Information on FDA-approved tests is available at http://www.fda.gov/CompanionDiagnostics.

Obtain a negative pregnancy test before starting therapy.
May exacerbate chemotherapy-induced neutropenia. May cause anemia, neutropenia, leukopenia, and febrile neutropenia.
May cause ↑ serum creatinine, AST, ALT, bilirubin and ↓ albumin.
May cause ↓ potassium and glucose and ↑ sodium and potassium.

Implementation

Phesgo has different dose and administration instructions than pertuzumab IV, trastuzumab IV, and SUBQ trastuzumab when administered alone. Do not use other drugs in place of Phesgo. Must always be administered by health care professional.
In patients receiving anthracycline-based regimen for early breast cancer, administer Phesgo following completion of the anthracycline. In patients receiving Phesgo for early breast cancer with docetaxel or paclitaxel, administer docetaxel or paclitaxel after Phesgo. In patients receiving Phesgo for metastatic breast cancer with docetaxel, administer docetaxel after Phesgo.
SUBQ Check label to make sure vial contains Phesgo and not IV pertuzumab, or IV trastuzumab, or SUBQ trastuzumab. Solution is clear to opalescent, and colorless to slightly brownish; do not administer solutions that are cloudy, discolored, or contain particulate matter. Do not dilute; do not shake. Attach 25–27 gauge 3/8–5/8 inch needle to syringe just before injection. Solution is stable for up to 4 hr at room temperature or 24 hr if refrigerated. Inject into thighs only; alternate between right and left thigh with each dose. Inject initial dose of 15 mL over 8 min. Inject maintenance dose of 10 mL over 5 min. Inject at least 1 inch from previous site and avoid areas where skin is red, bruised, tender, or hard. Inject other SUBQ medications in different sites.

Patient/Family Teaching

Explain purpose of Phesgo and regimen to patient.
Advise patient to notify health care professional immediately if signs and symptoms of cardiomyopathy (new onset or worsening shortness of breath, cough, swelling of ankles or legs, swelling of face, palpitations, weight gain >5 pounds in 24 hr, dizziness, loss of consciousness) or hypersensitivity and administration-related reactions (dizziness, nausea, chills, fever, vomiting, diarrhea, urticaria, swelling of face or neck, breathing problems, chest pain) occur.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception and to avoid breastfeeding for 7 mo after last dose. If Phesgo is administered during pregnancy, or if a patient becomes pregnant while receiving Phesgo or within 7 mo following last dose of Phesgo , health care providers and patients should immediately report Phesgo exposure to pharmacovigilance program at Genentech at 1-888-835-2555.

Evaluation/Desired Outcomes