pertuzumab/trastuzumab/hyaluronidase

High Alert

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).

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
OB:
Pregnancy
.

Use Cautiously in:

HF, uncontrolled hypertension, recent MI, arrhythmias, or 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);
Rep:
Women of reproductive potential
;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: Safety and effectiveness not established in children.

Adv. 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, ↑liver enzymes, constipation, diarrhea, dyspepsia, hypoalbuminemia, nausea, stomatitis, vomiting, weight loss, 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)

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.

Availability ⬆ ⬇

Solution for injection: pertuzumab 60 mg, trastuzumab 60 mg, and hyaluronidase 2000 units/mL; pertuzumab 80 mg, trastuzumab 40 mg, and hyaluronidase 2000 units/mL

Route/Dosage ⬆ ⬇

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

Neoadjuvant Treatment of Breast Cancer

SC (Adults ): Initial dose: Pertuzumab 1200 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 1st, 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

SC (Adults ): Initial dose: Pertuzumab 1200 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 1st, 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

SC (Adults ): Initial dose: Pertuzumab 1200 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.

US Brand Names ⬆ ⬇

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 effects:

Regression of breast cancer and metastases.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: HER2/neu receptor antagonists, monoclonal antibodies

Pharmacokinetics ⬆ ⬇

Pertuzumab

Absorption: 70% absorbed following SUBQ administration.

Distribution: Minimally distributed to tissues.

Metabolism/Excretion: Unknown.

Half-Life: Unknown.

Trastuzumab

Absorption: 80% absorbed following SUBQ administration.