Dr. Tripathy on Trastuzumab Deruxtecan Versus T-DM1 in HER2-Expressing Breast Cancers

Debu Tripathy, MD, professor of medicine and chair of the Department of Breast Medical Oncology at The University of Texas MD Anderson Cancer Center, discusses fam-trastuzumab deruxtecan-nxki (Enhertu) versus ado–trastuzumab emtansine (T-DM1; Kadcyla) in HER2-expressing breast cancers.

Certain characteristics of trastuzumab deruxtecan are distinct from T-DM1, says Tripathy. One of the principal features in the laboratory and preclinical models is that trastuzumab deruxtecan is water soluble. When the antibody-drug conjugate is internalized into the tumor cell, it is slowly released into the microenvironment and can diffuse back out of the cells, explains Tripathy. Because of this functionality, the agent may also be able to impact other neighboring cells.

This ability is important because HER2 is not uniformly expressed on all tumors cells; some cells may express HER2 at a higher level than others, says Tripathy. Sometimes, when patients develop resistance to HER2–targeted therapies, the resistant subclone that grows has lost HER2 expression. Because trastuzumab deruxtecan can bind to lower-expressing HER2 cells, such as HER2 1+/2+, the agent may have an advantage over T-DM1, concludes Tripathy.