Use of Pertuzumab for the Treatment of HER2-Positive Metastatic Breast Cancer
Targeting the human epidermal growth factor receptor (HER) family of tyrosine kinase receptors has proven to be effective as a therapeutic strategy for HER type 2 (HER2)-positive breast cancer. Since resistance to trastuzumab occurs relatively frequently, particularly in the metastatic setting, novel anti-HER2 targeted therapies with complementary and/or synergistic mechanisms of action have been under development. Pertuzumab, a HER2-targeted monoclonal antibody that prevents HER2 dimerisation, is the first of a class of promising targeted agents for the treatment of HER2-positive breast cancer.
A review of the biomedical literature published prior to February 2013 was conducted in English using PubMed. ClinicalTrials.gov was searched for appropriate clinical trials. The search terms used included breast neoplasm, pertuzumab, dimerisation, and HER2-positive. Abstracts of studies presented at the ASCO and ESMO Annual Meetings, and San Antonio Breast Cancer Symposium were also included.
Pertuzumab represents a novel anti-HER2 targeted therapy for HER2-positive breast cancers. In this article, we describe the mechanism of action of pertuzumab, as well as its drug development process and preclinical testing results. Based on the results of ancillary studies, dual inhibition using pertuzumab and trastuzumab was shown to be effective for the management of HER2-positive metastatic breast cancers pre-treated with trastuzumab-based therapy. For the first-line setting, the combination of both pertuzumab and trastuzumab with docetaxel (CLEOPATRA trial; clinical evaluation of pertuzumab and trastuzumab) has changed the paradigm of patient management.
Pertuzumab provided a more comprehensive inhibition of HER2-driven signalling pathways. When administered together with trastuzumab, pertuzumab represent a significant advancement for the treatment of HER2-positive metastatic breast cancer patients.
KeywordsDimerisation HER2 Metastatic breast cancer Pertuzumab
- 17.Marty M, Cognetti F, Maraninchi D, et al. Randomized phase ii trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol. 2005;23:4265–74.PubMedCrossRefGoogle Scholar
- 23.Cortes J, Fumoleau P, Bianchi GV, et al. Pertuzumab monotherapy after trastuzumab-based treatment and subsequent reintroduction of trastuzumab: activity and tolerability in patients with advanced human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2012;30:1594–600.PubMedCrossRefGoogle Scholar
- 41.Gianni L, Llado A, Bianchi G, et al. Open-label, phase II, multicenter, randomized study of the efficacy and safety of two dose levels of pertuzumab, a human epidermal growth factor receptor 2 dimerization inhibitor, in patients with human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2010;28:1131–7.PubMedCrossRefGoogle Scholar
- 44.Miles D, Baselga J, Amadori D, et al. Pertuzumab (p) in combination with trastuzumab (T) and docetaxel (D) in elderly patients with HER2-positive metastatic breast cancer in the Cleopatra study. Cancer Res. 2012;72(24 Suppl):P5-18-01 (Abstract).Google Scholar
- 45.Baselga J, Cortés J, Im S-A, et al. Biomarker analyses in Cleopatra: a phase iii, placebo-controlled study of pertuzumab in her2-positive, first-line metastatic breast cancer (mbc). Cancer Res. 2012;72(24 Suppl):S5-1 2012 (Abstract).Google Scholar
- 46.Datko F, D’Andrea G, Dickler M, et al. Phase II study of pertuzumab, trastuzumab, and weekly paclitaxel in patients with metastatic her2-overexpressing metastatic breast cancer. Cancer Res. 2012;72(24 Suppl):P5-18-20 (Abstract).Google Scholar
- 49.Ellis P, Barrios C, Im YH, et al. MARIANNE: a phase III, randomized, multicenter study of trastuzumab emtansine (T-DM1)± pertuzumab compared with trastuzumab plus taxane for first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive, progressive or recurrent locally advanced or metastatic breast cancer. J Clin Oncol. 2011;29:TPS102 (Abstract).Google Scholar
- 52.Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early her2-positive breast cancer (Neosphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13:25–32.PubMedCrossRefGoogle Scholar
- 54.Schneeweiss A, Chia S, Hickish T, et al. Neoadjuvant pertuzumab and trastuzumab concurrent or sequential with an anthracycline containing or concurrent with an anthracycline-free standard regimen: A randomized phase ii study (TRYPHAENA). Cancer Res. 2011;71(24 Suppl):S5–6 (Abstract).Google Scholar
- 56.NCCN clinical practice guidelines in oncology™. Breast cancer (online). http://wwwnccnorg/professionals/physician_gls/pdf/breastpdf (2012). Accessed 15 March 2013.