General Information

Perjeta (pertuzumab) is a HER2/neu receptor antagonist compound. It has been shown to augment anti-tumor activity as a complement to Herceptin, as the two medicines target different regions on the HER2 receptor.

Perjeta is specifically indicated for: 

• Use in combination with trastuzumab and 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.
• Use in combination with trastuzumab and 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 

The initial Perjeta 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.

MBC: Administer Perjeta, trastuzumab or trastuzumab hyaluronidaseoysk, and docetaxel every 3 weeks.

Neoadjuvant: Administer Perjeta, trastuzumab or trastuzumab hyaluronidase-oysk, and chemotherapy preoperatively every 3 weeks for 3 to 6 cycles.

Adjuvant: Administer Perjeta, trastuzumab or trastuzumab hyaluronidase-oysk, and chemotherapy postoperatively every 3 weeks for a total of 1 year (up to 18 cycles).

Mechanism of Action

Pertuzumab targets the extracellular dimerization domain (Subdomain II) 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. As a result, pertuzumab inhibits ligand-initiated intracellular signaling through two major signal 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. In addition, pertuzumab mediates antibody-dependent cell-mediated cytotoxicity (ADCC). The drug's anti-tumor activity is significantly augmented when administered in combination with Herceptin.

Side Effects

Adverse reactions associated with the use of Perjeta in combination with trastuzumab and docetaxel may include, but are not limited to, the following:

• diarrhea
• alopecia
• neutropenia
• nausea
• fatigue
• rash
• peripheral neuropathy

The Perjeta drug label comes with the following Black Box Warning: Left Ventricular Dysfunction: Perjeta can result in subclinical and clinical cardiac failure manifesting as decreased LVEF and CHF. Evaluate cardiac function prior to and during treatment. Discontinue Perjeta treatment for a confirmed clinically significant decrease in left ventricular function. Embryo-fetal Toxicity: Exposure to Perjeta can result in embryo-fetal death and birth defects. Advise patients of these risks and the need for effective contraception.

Clinical Trial Results

The FDA approval of Perjeta was based on the results of a randomized, multicenter, double-blind, placebo-controlled trial of 808 subjects with HER2-positive metastatic breast cancer. Subjects were randomized to receive placebo plus trastuzumab and docetaxel or Perjeta plus Herceptin (trastuzumab) and docetaxel. Randomization was stratified by prior treatment and geographic region. Perjeta was given intravenously at an initial dose of 840 mg, followed by 420 mg every three weeks thereafter. Herceptin was given intravenously at an initial dose of 8 mg/kg, followed by 6 mg/kg every three weeks thereafter. Subjects were treated with Perjeta and trastuzumab until progression of disease, withdrawal of consent, or unacceptable toxicity. Docetaxel was given as an initial dose of 75 mg/m2 by intravenous infusion every three weeks for at least six cycles. The docetaxel dose could be escalated to 100 mg/m2 at the investigator’s discretion if the initial dose was well tolerated. The study showed subjects who received Perjeta in combination with Herceptin and docetaxel chemotherapy experienced a 38% reduction in the risk of their disease worsening or death compared to those who received Herceptin and chemotherapy plus placebo (HR=0.62; p<0.0001). The study demonstrated a 6.1 month improvement in median progression-free survival (PFS) in subjects treated with Perjeta compared to those who received Herceptin and chemotherapy plus placebo (median PFS 18.5 vs. 12.4 months).