Dr. Weiner on the T-DM1 Mechanism of Action

Louis M. Weiner, MD, Director, Lombardi Comprehensive Cancer Center, Associate Vice President, Georgetown University Medical Center, discusses the mechanism of action for the antibody drug conjugate trastuzumab emtansine (T-DM1), which combines the anti-HER2 antibody trastuzumab (Herceptin) with the cytotoxin mertansine, also called DM1.

Weiner explains that T-DM1 works in several different ways. First, trastuzumab selectively binds to HER2 receptors and is internalized by the cancer cell. In addition to the antitumor activity initiated by trastuzumab, once internalized by the cancer cell, DM1 is selectively liberated causing apoptosis.

T-DM1 demonstrated an impressive survival benefit in the phase III EMILIA trial, which compared T-DM1 to capecitabine plus lapatinib for women with HER2-positive locally advanced or metastatic breast cancer.