Pertuzumab. Perjeta®

Abstract

Human epidermal growth factor receptor (HER) 2, a transmembrane tyrosine-kinase receptor, is a member of the epidermal growth-factor receptor (EGFR) family. In approximately 20% of breast tumors HER2 is amplified and/or overexpressed. While HER2-positive tumors represent an aggressive subtype of breast cancer, the prognosis of these neoplasms has changed dramatically since the introduction of monoclonal antibodies like trastuzumab, the first one used in this setting. A number of patients develop primary and secondary resistance to trastuzumab and several therapeutic strategies to combat this issue have emerged. A common approach is to initiate dual HER2 blockade by combining two different drugs against HER2, such as trastuzumab and pertuzumab. Pertuzumab prevents HER2:HER3 dimer formation and subsequent HER3-mediated signaling. The theoretically complementary mechanisms of pertuzumab and trastuzumab imply a greater efficacy when used together, as they would provide a more complete block of downstream signaling. The use of pertuzumab is approved for HER2-positive metastatic or locally recurrent breast cancer, in combination with chemotherapy and trastuzumab, where it prolongs progression free survival, overall survival and objective response rate. The benefits of its use for locally advanced resectable breast cancer are also promising, improving complete pathologic responses. In general, pertuzumab is safe and well tolerated, and it appears to have low cardiac toxicity. In conclusion, it is a fact that pertuzumab has transformed the approach to HER2-positive disease and further combination strategies will incorporate it as an essential drug.