Trastuzumab-DM1: A Review of the Novel Immuno-Conjugate for HER2- Overexpressing Breast Cancer

Abstract

Trastuzumab is a monoclonal antibody targeted against the HER2 tyrosine kinase receptor. Although trastuzumab is a very active agent in HER2-expressing breast cancer, the majority of patients with metastatic HER2 overexpressing breast cancer who initially respond to trastuzumab develop resistance within one year of initiation of treatment, and in the adjuvant setting, progress despite trastuzumab-based therapy. The immuno-conjugate Trastuzumab-DM1 (T-DM1) was designed to combine the biological activity of trastuzumab with the targeted delivery of a highly potent antimicrotubule agent, DM1, a maytansine derivative, to HER2-expressing breast cancer cells. T-DM1 is the first immuno-conjugate with a non-reducible thioether linker in clinical trials. Here, we summarize evidence from pre-clinical studies, analyze clinical data, and discuss the potential clinical implications of T-DM1.