Pertuzumab

Pertuzumab is a humanized monoclonal antibody that specifically binds to the extracellular dimerization domain (subdomain II) of the growth factor receptor protein HER2 (Human Epidermal growth factor Receptor 2, CD340). Pertuzumab prevents the HER2 receptor from dimerizing with other HER receptors(EGFR, HER3, HER4) on the surface of the cells. This blocks signalling pathways, which can lead to growth inhibition and apoptosis of the cell. Furthermore, pertuzumab is a mediator for antibody-dependent cell-mediated cytotoxicity.(ADCC, antibody dependent cellular cytotoxicity). Pertuzumab binds to a different epitope of the HER2 receptor than trastuzumab.

ErbB receptors, a family of transmembrane receptor tyrosine kinases and in particular HER2, have been identified as an important target in the fight against breast cancer. ErbB receptors mediate their proliferative signals via a major cytoprotective signal transduction pathway involving adaptor proteins such as GRB2 and SHC, GTP exchange factors such as SOS, phospholipase Cγ (PLCγ), Ras, protein kinase C (PKC), Raf, MAPK, and PI-3 kinase-dependent signaling pathways. These signal transduction pathways directly or indirectly affect cell cycle control and transcriptional regulation, which trigger the biosynthetic machinery and cell proliferation. Thus, signal transduction by HER2 plays a key role, particularly in tumor growth and cell differentiation.

In clinical trials, pertuzumab in combination with trastuzumab and docetaxel has shown a significant increase in progression-free survival and overall survival in patients with HER2-positive breast cancer compared with the previous standard therapy, without increasing the incidence of adverse cardiac events.

Pertuzumab is indicated for use in combination with trastuzumab and docetaxel in adult patients with HER2-positive metastatic or locally recurrent unresectable breast cancer who have not previously received anti-HER2 therapy or chemotherapy to treat their metastatic disease. Pertuzumab is also indicated in combination with trastuzumab and chemotherapy in adult patients for neoadjuvant treatment of HER2-positive, locally advanced, inflammatory or early breast cancer with a high risk of recurrence.

EU approval: October 3, 2013.

At the beginning of therapy, 840 mg pertuzumab is administered together with 8 mg/kg trastuzumab and 75 mg/m2 docetaxel. After three weeks, 420 mg pertuzumab is administered together with 6 mg/kg trastuzumab and 75 or 100 mg/m2 docetaxel.

Changes in blood values:

• Neutropenia
• febrile neutropenia
• Leukopenia
• Anemia

Nasopharyngitis, hypersensitivity/anaphylactic reaction, infusion reaction, insomnia, loss of appetite, peripheral neuropathy, headache, dysgeusia, cough, diarrhea, vomiting, stomatitis, mucositis, nausea, constipation, indigestion, effluvium and alopecia, exanthema, nail changes, myalgia, arthralgia, pain, edema, fever, fatigue, asthenia.

Furthermore, a tendency to folliculitis and purulent paronychia has been reported (Mortimer J et al. 2014)

Perjeta®

Prior to treatment with these antibodies, it is necessary to detect the corresponding HER receptor in the tumor cells.

1. An J et al (2019) Toxicology of Trastuzumab: An Insight into Mechanisms of Cardiotoxicity. Curr Cancer Drug Targets 19:400-407.
2. Baselga J et al (2012) (CLEOPATRA = CLinical Evaluation Of Pertuzumab And Trastuzumab). N. Engl J Med 366: 109.
3. Barish R et al (2019) Trastuzumab-Induced Cardiomyopathy. Cardiol Clin 37: 407-418.

4. Mortimer J et al (2014) Skin/nail infections with the addition of pertuzumab to trastuzumab-based chemotherapy. Breast Cancer Res Treatment 148:563-570.

5. Swain SM et al (2013) (CLEOPATRA = CLinical Evaluation Of Pertuzumab And Trastuzumab). Lancet Oncol 14: 461.