Pertuzumab is a HER2/neu receptor antagonist indicated for the following uses:

• In combination with trastuzumab and docetaxel for the treatment of patients with HER2-positive metastatic breast cancer (MBC) who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.
• In combination with trastuzumab and docetaxel as neoadjuvant treatment for patients with HER2-positive locally advanced, inflammatory, or early-stage breast cancer (tumor >2 cm or node-positive) as part of a complete treatment regimen for early breast cancer. This indication is based on improved pathological complete response rates. However, no data are available showing improvement in event-free survival or overall survival.

Limitations of Use: The safety of Pertuzumab as part of a doxorubicin-containing regimen has not been established. The safety of Pertuzumab use beyond 6 cycles in early breast cancer has also not been established.

Pertuzumab is a recombinant humanized monoclonal antibody that targets the extracellular dimerization domain (Subdomain II) of the human epidermal growth factor receptor 2 (HER2). By binding to this domain, it prevents ligand-dependent heterodimerization of HER2 with other HER family receptors such as EGFR, HER3, and HER4. As a result, Pertuzumab inhibits intracellular signaling through two major pathways: the MAP kinase pathway and the PI3K pathway. Inhibition of these pathways leads to cell growth arrest and induction of apoptosis. In addition, Pertuzumab can mediate antibody-dependent cell-mediated cytotoxicity (ADCC), contributing to tumor cell destruction.

For intravenous infusion only. It should not be administered as an intravenous push or bolus. The initial Pertuzumab dose is 840 mg administered as a 60-minute intravenous infusion, followed every 3 weeks thereafter by 420 mg administered as a 30 to 60 minute intravenous infusion.

Metastatic breast cancer: Pertuzumab should be administered with Trastuzumab and Docetaxel by intravenous infusion every 3 weeks.

Neoadjuvant: Pertuzumab should be administered with Trastuzumab and Docetaxel by intravenous infusion preoperatively every 3 weeks for 3 to 6 cycles.

Pediatric Use: Safety and effectiveness of Pertuzumab have not been established in pediatric patients.

Pertuzumab should be administered as an intravenous infusion only. It should not be administered as an intravenous push or bolus. Pertuzumab should not be used with other drugs.

Patients who receive anthracycline therapy after discontinuing Pertuzumab may have an increased risk of cardiac dysfunction due to the long washout period of Pertuzumab. If possible, anthracycline-based treatment should be avoided for up to 7 months after stopping Pertuzumab. If anthracyclines are required, cardiac function should be closely monitored.

Pertuzumab is contraindicated in patients with known hypersensitivity to pertuzumab or any of its excipients.

Left Ventricular Dysfunction: Pertuzumab may cause subclinical or clinical cardiac failure, including congestive heart failure (CHF) and reduced left ventricular ejection fraction (LVEF). Cardiac function should be assessed before and during treatment. Treatment should be discontinued if clinically significant reduction in LVEF is confirmed.

Embryo-fetal Toxicity: Exposure during pregnancy may cause fetal death or congenital abnormalities. Animal studies have shown oligohydramnios, delayed kidney development, and fetal death. Patients should be informed about these risks and advised to use effective contraception.

Metastatic Breast Cancer: Common adverse effects (>30%) include diarrhea, hair loss (alopecia), neutropenia, nausea, fatigue, rash, and peripheral neuropathy when used with trastuzumab and docetaxel.

Neoadjuvant Breast Cancer Treatment:

• With trastuzumab + docetaxel: alopecia, diarrhea, nausea, neutropenia
• After FEC regimen: fatigue, alopecia, diarrhea, nausea, vomiting, neutropenia
• With TCH regimen: fatigue, alopecia, diarrhea, nausea, vomiting, neutropenia, thrombocytopenia, anemia

Pregnancy Category D. There are no adequate controlled studies in pregnant women. If Pertuzumab is used during pregnancy or pregnancy occurs within 7 months after the last dose, the patient should be informed about potential fetal risks.

It is unknown whether Pertuzumab passes into breast milk. However, human IgG may be present in breast milk. Because of potential serious risks to the infant, a decision should be made either to discontinue breastfeeding or discontinue the drug, considering its half-life and maternal importance.

Left Ventricular Dysfunction: LVEF should be monitored regularly and treatment should be withheld if necessary.

Embryo-fetal Toxicity: May cause fetal harm if used during pregnancy.

Infusion-related reactions: Patients should be monitored for reactions during infusion. If severe reaction occurs, infusion should be slowed, interrupted, or stopped with appropriate treatment.

Hypersensitivity/Anaphylaxis: Patients should be closely monitored. In case of severe reaction, infusion must be stopped immediately and emergency treatment provided.

Targeted cancer therapy

Store the vials in a refrigerator at 2°C to 8°C until use. Keep the vial in the outer carton to protect it from light.