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Pertuzumab: A Review of Its Use for First-Line Combination Treatment of HER2-Positive Metastatic Breast Cancer

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Abstract

Pertuzumab (Perjeta®) is a humanized anti-HER2 monoclonal antibody that binds to the extracellular dimerization subdomain of the HER2 receptor and reduces HER2 intracellular signalling by preventing HER2 from forming heterodimers with other HER receptors. Inhibition of HER2 signalling results in a reduction of tumour cell proliferation, invasiveness and survival. Pertuzumab and trastuzumab bind to different sites on the HER2 receptor and have complementary antitumour activities; they act synergistically in inhibiting the growth of HER2-overexpressing breast cancer cell lines in vitro. The efficacy of intravenous pertuzumab (840 mg loading dose, then 420 mg every 3 weeks) in combination with trastuzumab plus docetaxel in the first-line treatment of HER2-positive metastatic breast cancer was demonstrated in the randomized, double-blind, placebo-controlled, multinational, phase III CLEOPATRA trial. Pertuzumab in combination with trastuzumab and docetaxel significantly increased independently assessed median progression-free survival (primary endpoint), objective response rate and overall survival compared with placebo in combination with trastuzumab and docetaxel. Pertuzumab had an acceptable tolerability profile when added to trastuzumab and docetaxel in the pivotal CLEOPATRA trial. Thus, pertuzumab is a valuable addition to the growing list of anti-HER2 targeted therapies for breast cancer.

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Disclosure

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the author on the basis of scientific and editorial merit.

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    Paul L. McCormack

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Correspondence to Paul L. McCormack.

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The manuscript was reviewed by: A. Antonelli, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; A.U. Buzdar, Department of Breast Medical Oncology, MD Anderson Cancer Center, University of Texas, Houston, TX, USA; P. Fumoleau, Medical Oncology Department, Centre Georges-François Leclerc, Dijon, France.

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McCormack, P.L. Pertuzumab: A Review of Its Use for First-Line Combination Treatment of HER2-Positive Metastatic Breast Cancer. Drugs 73, 1491–1502 (2013). https://doi.org/10.1007/s40265-013-0109-0

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