Novel approaches to target HER2-positive breast cancer: trastuzumab emtansine

Abstract

The human epidermal growth factor receptor 2 (HER2) is overexpressed in 20% of breast carcinomas. Prior to the development of targeted therapies, HER2-positive breast cancer was associated with more aggressive disease and poor prognosis. Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that results from the combination of trastuzumab and DM1, a derivative of the antimicrotubule agent maytansine. This molecule has the ability to enhance cytotoxic drug delivery to specifically targeted cells that overexpress HER2, therefore, maximizing efficacy while sparing toxicity. In recent years, T-DM1 has shown to improve outcomes in metastatic HER2-positive breast cancer that is resistant to trastuzumab. In addition, T-DM1 is currently being tested in the neoadjuvant and adjuvant settings to identify patients who may benefit from this therapy. This review focuses on the mechanism of action, early and late-phase clinical trials, and ongoing studies of T-DM1 in HER2-positive breast cancer.

Keywords:

• T-DM1
• trastuzumab emtansine
• HER2-positive breast cancer
• metastatic breast cancer
• targeted therapies

Acknowledgments

We want to thank The University of Iowa Libraries for supporting this publication.

Disclosure

Maximo de la Vega and Enrique Díaz-Cantón are members of the advisory board of Roche. The other authors report no conflicts of interests in this work.