Dr. Modi on Trastuzumab Deruxtecan in HER2-low Breast Cancer

Shanu Modi, MD, medical oncologist, attending physician, Memorial Sloan Kettering Cancer Center, discusses the significance of the FDA approval of the antibody-drug conjugate fam-trastuzumab deruxtecan-nxki (Enhertu) in patients with HER2-low breast cancer.

On August 5th, 2022, the FDA approved trastuzumab deruxtecan in patients with unresectable or metastatic HER2-low breast cancer. The regulatory decision was based on findings from the phase 3 DESTINY-Breast04 trial (NCT03734029), in which treatment with trastuzumab deruxtecan demonstrated a median progression-free survival of 10.1 months vs 5.4 months with chemotherapy in patients with hormone receptor–positive, HER2-low metastatic breast cancer. The agent also elicited a median overall survival of 23.9 months vs 17.5 months with chemotherapy.

Breast cancers have historically been classified in a binary fashion, as either HER2-positive or HER2-negative, Modi says. Although breast cancers with high levels of the HER2 protein are traditionally considered HER2-positive and all other breast cancers are considered HER2-negative, some tumors in the HER2-negative population still express HER2 at low levels, Modi explains. However, no current HER2-targeted therapies have been effective in this HER2-low category of breast cancer, Modi notes.

Trastuzumab deruxtecan is the first active HER2-targeted therapy in the HER2-low breast cancer population, and it is much more effective than the other options these patients have received in the past, Modi says. The FDA approval of this agent is a positive development for a large proportion of patients with metastatic breast cancer, Modi concludes.