The antibody-drug conjugate Enhertu (fam-trastuzumab deruxtecan), approved in 2019 for the treatment of metastatic breast cancer with high HER2 expression, has now been ap- proved for people with low HER2 levels as well.

Breast cancer is classified by the type of receptors on tumors. Around 15% of patients have a high level of HER2, a receptor for a protein that promotes cell growth. But some 60% of people who were traditionally classified as HER2-negative actually have some HER2 receptors, a group now defined as HER2-low.

The Phase III DESTINY-Breast04 trial included 557 previously treated women with HER2-low metastatic breast cancer. They were randomly assigned to receive Enhertu or their physician’s choice of chemotherapy. Antibody-drug conjugates like Enhertu use monoclonal antibodies to deliver toxic chemotherapy drugs directly to tumors.

Among women with hormone- receptor-positive, HER2-low tumors, the median overall survival time was 23.9 months in the Enhertu group versus 17.5 months in the chemotherapy group. Enhertu reduced the risk of disease progression by 49% and the risk of death by 36%. The presentation earned a standing ovation, and some experts say the results are “practice changing.”

“Our study shows that trastuzumab deruxtecan may be a new and highly effective targeted therapy option avail- able for this newly defined patient population,” says investi- gator Shanu Modi, MD, of Memo- rial Sloan Kettering Cancer Cen- ter. The results could also be relevant for people with other types of HER2-low cancer.