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Review
. 2014 May 16:6:509-21.
doi: 10.2147/IJWH.S47357. eCollection 2014.

Pertuzumab in human epidermal growth-factor receptor 2-positive breast cancer: clinical and economic considerations

Nathan Wd Lamond  1 , Tallal Younis  1
Affiliations
Review

Pertuzumab in human epidermal growth-factor receptor 2-positive breast cancer: clinical and economic considerations

Nathan Wd Lamond et al. Int J Womens Health. .

Abstract

In the absence of specific therapy, the 15%-20% of breast cancers demonstrating human epidermal growth-factor receptor 2 (HER2) protein overexpression and/or gene amplification are characterized by a more aggressive phenotype and poorer prognosis compared to their HER2-negative counterparts. Trastuzumab (Herceptin), the first anti-HER2-targeted therapy, has been associated with improved survival outcomes in HER2-positive breast cancer. However, many patients with early stage disease continue to relapse, and metastatic disease remains incurable. In order to further improve these outcomes, several novel HER2-targeted agents have recently been developed. Pertuzumab (Perjeta), a monoclonal antibody against the HER2 dimerization domain, has also been associated with improved patient outcomes in clinical trials, and has recently been approved in combination with chemotherapy and trastuzumab for neoadjuvant therapy of early stage, HER2-positive breast cancer and first-line treatment of metastatic disease. This review briefly summarizes pertuzumab's clinical development as well as the published evidence supporting its use, and highlights some of the currently unanswered questions that will influence pertuzumab's incorporation into clinical practice.

Keywords: HER2/neu; clinical trials; drug development; novel therapies; targeted anticancer therapy.

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Figures

Figure 1
Figure 1
Mechanism of action for pertuzumab, which binds to HER2 epitope II, preventing both homo-and heterodimerization, whereas trastuzumab binds to epitope IV. Abbreviation: HER, human epidermal growth-factor receptor.
Figure 2
Figure 2
Landmark trials of pertuzumab in the adjuvant, neoadjuvant, and metastatic settings. The chemotherapy regimens utilized include docetaxel (CLEOPATRA and preoperatively in NEOSPHERE), fluorouracil/epirubicin/cyclophosphamide (postoperative in NEOSPHERE), and other center-specific approved regimens (Aphinity). Targeted therapies were delivered for a total of 1 year in the neoadjuvant and adjuvant trials or until progression in the metastatic trial. Abbreviations: Chemo, chemotherapy; T, trastuzumab; P, pertuzumab.
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