PERJETA

What it is

Perjeta contains pertuzumab. Perjeta is supplied as a 420 mg concentrate for intravenous infusion. Pertuzumab binds to the extracellular dimerization domain of the human epidermal growth factor receptor 2 protein (HER2) and thereby blocks ligand-dependent heterodimerization of HER2 with other HER family members, including EGFR, HER3 and HER4. It inhibits ligand-initiated intracellular signalling through two major signal pathways, mitogen-activated protein (MAP) kinase and phosphoinositide 3-kinase (PI3K).

Approved indications

— Neoadjuvant treatment of patients with HER2-positive inflammatory or locally advanced, or early stage (either greater than 2 cm in diameter or node positive) breast cancer, in combination with trastuzumab and chemotherapy, 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, in combination with trastuzumab and chemotherapy. — Treatment of patients with metastatic HER2-positive breast cancer who have not received prior anti-HER2 therapy or chemotherapy for their metastatic disease, in combination with trastuzumab and docetaxel.

Dosing overview

The recommended initial dose of Perjeta is 840 mg, administered as a 60 minute intravenous infusion, followed by, every 3 weeks, a 420 mg dose administered over 30–60 minutes. Patients must have a HER2-positive tumour status, defined as a score of 3+ by immunohistochemistry (IHC) and/or a ratio of ≥2.0 by in situ hybridization (ISH). Perjeta and trastuzumab should be administered sequentially and not mixed in the same infusion bag. Perjeta and trastuzumab can be given in any order. In the neoadjuvant setting it is recommended that patients are treated with Perjeta for three to six cycles depending on the regimen chosen, in combination with trastuzumab and chemotherapy. In the adjuvant setting, Perjeta should be administered in combination with trastuzumab for a total of one year (maximum 18 cycles or until disease recurrence, or unmanageable toxicity, whichever occurs first).

Key safety warnings

Decreases in left ventricular ejection fraction (LVEF) have been reported with medicinal products that block HER2 activity, including Perjeta. The incidence of symptomatic left ventricular systolic dysfunction (congestive heart failure) was higher in patients treated with Perjeta in combination with trastuzumab and chemotherapy compared with trastuzumab and chemotherapy. Patients who have received prior anthracyclines or prior radiotherapy to the chest area may be at higher risk of LVEF declines. Assess LVEF prior to initiation of Perjeta and at regular intervals during treatment with Perjeta (for example, once during neoadjuvant treatment and every 12 weeks in the adjuvant or metastatic setting) to ensure that LVEF is within normal limits. Perjeta has been associated with infusion related reactions, including events with fatal outcomes. Close observation of the patient during, and for 60 minutes after the first infusion and during, and for 30 minutes following subsequent infusions, is recommended following the administration of Perjeta. Severe hypersensitivity reactions, including anaphylaxis and events with fatal outcomes have been observed in patients treated with Perjeta. Patients treated with Perjeta, trastuzumab and docetaxel are at increased risk of febrile neutropenia compared with patients treated with placebo, trastuzumab and docetaxel. This may be associated with a higher incidence of mucositis and diarrhoea in Perjeta-treated patients. Perjeta may elicit severe diarrhoea. Diarrhoea is most frequent during concurrent administration with taxane therapy.

Contraindications

Perjeta is contraindicated in patients with known hypersensitivity to pertuzumab, Chinese hamster ovary cell proteins or to any other component of the product.

PBS listing

Perjeta is listed on the PBS as a solution for intravenous infusion 420 mg in 14 mL under 4 items with authority required restriction. The ex-manufacturer price is A$2772.81.

Regulatory history

Perjeta (pertuzumab) was first registered on the ARTG on 6 May 2013. The initial approval was for use in combination with trastuzumab and docetaxel for patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for their metastatic disease. In November 2017, the PBAC recommended listing for adjuvant treatment of HER2-positive early breast cancer, and recommended a change to allow pertuzumab to be used in combination with trastuzumab and chemotherapy for the neoadjuvant treatment of HER2-positive early breast cancer. In March 2025, the PBAC recommended new listing for HER2-positive locally advanced, inflammatory or early stage breast cancer in the neoadjuvant treatment setting.