Pertuzumab for the treatment of patients with previously untreated HER2-positive metastatic breast cancer

Abstract

Pertuzumab is a humanized monoclonal antibody directed at the dimerization domain of the receptor tyrosine-protein kinase erbB-2 (HER2) receptor. It possesses a unique and complimentary mechanism of action compared to trastuzumab, which has historically been the cornerstone of therapy for HER2-amplified breast cancer. Clinical trials demonstrate improved outcomes, with minimal increases in toxicity with the addition of pertuzumab to trastuzumab in patients with HER2-positive metastatic breast cancer, indicating the advantage of dual HER2 receptor blockade. Pertuzumab is approved as first-line therapy in combination with trastuzumab and docetaxel for HER2-positive metastatic breast cancer, with future opportunities to investigate its efficacy in other stages of breast cancer, as well as in the treatment of other malignancies.

Figure 1

Heterodimerization of receptor tyrosine-protein kinase erbB-2 (HER2) and erbB-3 (HER3) leads to intracellular downstream signaling that leads to oncologic proliferation. Pertuzumab binds to the dimerization arm (domain II) of HER2 with high affinity, stertically hindering HER2 signaling by inhibiting interactions with HER3. Alternatively, trastuzumab binds to domain IV, inhibiting HER2 function. The combination treatment with pertuzumab and trastuzumab therefore acts as complementary dual blockade of the HER2 receptor, leading to greater efficacy than that with either agent alone. ECD, extracellular domain; ICD, intracellular domain.