Oncofocus Test Kit
includes suggestions for Pertuzumab
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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 the first-line treatment of HER2+ metastatic breast cancer in combination with trastuzumab and docetaxel.
Perjeta is supplied as a 420 mg/14 mL single-use vial for intravenous infusion. The recommended initial 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.
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).
Adverse reactions associated with the use of Perjeta in combination with trastuzumab and docetaxel may include, but are not limited to, the following:
- peripheral neuropathy
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.