Pharmacokinetics, pharmacodynamics and clinical efficacy of pertuzumab in breast cancer therapy

Introduction: Pertuzumab is a recombinant, humanized monoclonal antibody that binds to the dimerization domain of human epidermal growth factor receptor 2 (HER2), inhibiting the heterodimerization of HER2 with other HER receptors. It has shown synergy with trastuzumab in preclinical studies, and has led to a significant prolongation of progression-free and overall survival compared with placebo when added to trastuzumab and docetaxel for the first-line treatment of HER2-positive metastatic breast cancer (BC).Areas covered: The HER family of receptors and their pathways, pertuzumab pharmacodynamics and preclinical activity, results from the main clinical trials, new drug combinations being developed, and predictors of response are discussed.Expert opinion: Pertuzumab represents an important anti-HER2 agent that differs from, but is synergistic with, trastuzumab. It is already a standard of care in the first-line treatment of HER2-positive metastatic BC, and studies are ongoing to define its role in the adjuvant setting. It is now imperative to identify which tumors need dual HER2 targeting and to study the activity of pertuzumab in combination with other HER-targeted agents, including anti-HER1, -HER3 or -HER4, which could also prove useful in HER2-normal cancers. Potential competitors are anti-HER3 antibodies and bi- or tri-specific antibodies. Development in combination with phosphoinositide 3-kinase inhibitors or with anti PD-L1 is warranted.