Hyaluronidase (human recombinant), Pertuzumab and Trastuzumab

PHESGO is a combination of pertuzumab and trastuzumab, HER2/neu receptor antagonists, and hyaluronidase, an endoglycosidase, indicated for: Use in combination with 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. Use in combination with 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.

Pertuzumab targets the extracellular dimerization domain (subdomain II) of HER2 and, thereby, blocks ligand-dependent heterodimerization of HER2 with other HER family members, including EGFR, HER3 and HER4. As a result, pertuzumab inhibits ligand-initiated intracellular signaling through two major signaling pathways, mitogen-activated protein (MAP) kinase and phosphoinositide 3-kinase (PI3K). Inhibition of these signaling pathways can result in cell growth arrest and apoptosis, respectively. Trastuzumab binds to subdomain IV of the extracellular domain of the HER2 protein to inhibit the ligand-independent, HER2 mediated cell proliferation and PI3K signaling pathway in human tumor cells that overexpress HER2.

For subcutaneous use in the thigh only. PHESGO has different dosage and administration instructions than intravenous pertuzumab and trastuzumab products. Do not administer intravenously. Perform HER2 testing using FDA-authorized tests by laboratories with demonstrated proficiency. The initial dose of PHESGO is 1,200 mg pertuzumab, 600 mg trastuzumab, and 30,000 units hyaluronidase administered subcutaneously over approximately 8 minutes, followed every 3 weeks by a dose of 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase administered subcutaneously over approximately 5 minutes. Neoadjuvant: administer PHESGO by subcutaneous injection every 3 weeks and chemotherapy by intravenous infusion preoperatively for 3 to 6 cycles.

PHESGO is contraindicated in patients with known hypersensitivity to pertuzumab, or trastuzumab, or hyaluronidase, or to any of its excipients.

Boxed warning: Cardiomyopathy: PHESGO administration can result in subclinical and clinical cardiac failure manifesting as CHF, and decreased LVEF, with greatest risk when administered concurrently with anthracyclines. Evaluate cardiac function prior to and during treatment. Discontinue PHESGO for cardiomyopathy. Embryo-fetal Toxicity: Exposure to PHESGO can result in embryo-fetal death and birth defects. Exacerbation of Chemotherapy-Induced Neutropenia. Hypersensitivity and Administration-Related Reactions (ARRs): Monitor patients for systemic hypersensitivity reactions. Permanently discontinue PHESGO in patients who experience anaphylaxis or severe hypersensitivity reactions.

The following adverse reactions are discussed in greater detail in other sections of the label: Cardiomyopathy Embryo-Fetal Toxicity Pulmonary Toxicity Exacerbation of Chemotherapy-Induced Neutropenia Hypersensitivity and Administration-Related Reactions Neoadjuvant and Adjuvant Treatment of Breast Cancer The most common adverse reactions (>30%) with PHESGO were alopecia, nausea, diarrhea, anemia, and asthenia. Metastatic Breast Cancer (based on intravenous pertuzumab ) The most common adverse reactions (> 30%) with pertuzumab in combination with trastuzumab and docetaxel were diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and peripheral neuropathy.

Patients who receive anthracycline after stopping PHESGO may be at increased risk of cardiac dysfunction because of PHESGO's long washout period. If possible, avoid anthracycline-based therapy for up to 7 months after stopping PHESGO. If anthracyclines are used, carefully monitor the patient's cardiac function.

Store PHESGO vials in the refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze. Do not shake.