Pertuzumab (PERJETA®)
Agent Description
Pertuzumab is a recombinant humanized monoclonal antibody that targets the extracellular dimerization domain (subdomain II) of the human epidermal growth factor receptor 2 protein (HER2). Pertuzumab is produced by recombinant DNA technology in a mammalian cell (Chinese Hamster Ovary) culture containing the antibiotic gentamicin. Gentamicin is not detectable in the final product. Pertuzumab has an approximate molecular weight of 148 kDa. Pertuzumab is a sterile, clear to slightly opalescent, colorless to pale brown liquid for intravenous infusion. Each single use vial contains 420 mg of pertuzumab at a concentration of 30 mg/mL in 20 mM L-histidine acetate (pH 6.0), 120 mM sucrose and 0.02% polysorbate 20.
Mechanism of Action
Pertuzumab targets the extracellular dimerization domain (subdomain II) of the human epidermal growth factor receptor 2 protein (HER2). It 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, 444 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). While pertuzumab alone inhibited the proliferation of human tumor cells, the combination of pertuzumab and trastuzumab augmented anti-tumor activity in HER2-overexpressing xenograft models.
Classification
Antineoplastic agent; monoclonal antibody
Molecular Target
HER2/neu
Monograph
Approved Indications
- Pertuzumab is indicated for use in combination with trastuzumab and docetaxel for the treatment of patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.
- Pertuzumab is indicated for use in combination with trastuzumab and docetaxel for the 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. This indication is based on demonstration of an improvement in pathological complete response rate. No data are available demonstrating 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 administered for greater than 6 cycles for early breast cancer has not been established.
View the pertuzumab package insert (PDF).
Studies of Interest
Areas NOT of Interest
- Combinations with ado-trastuzumab emtansine
- Combinations with bevacizumab
- Combinations with biosimilar trastuzumab
- Novel combinations in the absence of phase I data
- Studies that are answering another company’s development or medical questions where pertuzumab plus trastuzumab is already standard of care
Information collaborator would like included in investigator proposals
N/A
Genentech supports non-clinical research proposals through a separate mechanism. Please visit Genentech's Outgoing Material Transfer Agreement (MTA) Program to submit a request for a Genentech agent for non-clinical work.