Subcutaneous trastuzumab: development of a new formulation for treatment of HER2-positive early breast cancer

Trastuzumab is a monoclonal antibody directed against the human epidermal growth factor receptor 2 (HER2). HER2 is amplified or overexpressed in about 15% of breast cancers and is associated with aggressive disease. Clinical benefits of trastuzumab have been established in the treatment of both early and metastatic HER2-positive breast cancer. Patients with HER2-positive early breast cancer have to be treated with trastuzumab for one year in combination with and sequentially after chemotherapy. This requires that trastuzumab is intravenously infused over 30–90 minutes every 3 weeks for one year which is time-consuming for both the patient and the health care provider. Consequently, a subcutaneous formulation of trastuzumab using a recombinant human hyaluronidase has been developed. Recombinant human hyaluronidase transiently increases absorption and dispersion in the subcutaneous space of large therapeutic proteins, such as monoclonal antibodies, allowing subcutaneous administration of trastuzumab in about 5 minutes. Thus, subcutaneous trastuzumab could represent a new treatment option that could have benefit to both the patient and the health care system. This review focuses on the development of the subcutaneous trastuzumab formulation and analyzes clinical trials assessing the pharmacokinetics, efficacy, and safety of this new formulation.