Dr. Fernandez on the Utility of Trastuzumab Deruxtecan in HER2-Low Breast Cancer

Aileen I. Fernandez, PhD, postdoctoral fellow, Yale School of Medicine, discusses the utility of fam-trastuzumab deruxtecan-nxki (Enhertu) in HER2-low breast cancer.

Trastuzumab deruxtecan targets HER2 and has demonstrated efficacy in patients who have low levels of HER2 expression, Fernandez says. Trastuzumab (Herceptin) has utility in patients with high levels of HER2 expression, Fernandez explains. However, if patients have immunohistochemistry 0 or 1+ disease, they won’t respond to trastuzumab. 

Trastuzumab deruxtecan is an antibody-drug conjugate comprised of an anti-HER2 antibody, a cleavable linker, and a topoisomerase inhibitor, Fernandez continues. If trastuzumab deruxtecan identifies any level of HER2 expression, it is then able to latch onto the cell and deliver its cytotoxic payload, Fernandez says. Then, it goes back into the bloodstream targeting the neighboring cells that do not have HER2 expression, which is why it has activity in HER2-low disease, Fernandez concludes