A New Option for Breast Cancer Patients

The FDA approved a HER2-targeted therapy for the treatment of breast tumors with low HER2 expression. 

The U.S. Food and Drug Administration (FDA) has approved fam-trastuzumab deruxtecan-nxki (Enhertu) for the treatment of adult patients with unresectable or metastatic breast tumors that express the receptor HER2 at low levels. The treatment is intended for patients who have previously received chemotherapy. 

Fam-trastuzumab deruxtecan-nxki is a therapy called an antibody-drug conjugate. It consists of a toxic drug (deruxtecan-nxki) conjugated to an antibody (fam-trastuzumab) that targets a protein expressed strongly on the surface of cancer cells. When the antibody portion binds to its target, the cell internalizes the therapy and releases the drug, allowing it to kill the cell. 

Fam-trastuzumab deruxtecan-nxki targets the growth factor receptor HER2, which is commonly overexpressed in breast cancer. While it has been approved to treat patients with breast cancer, non-small cell lung cancer, gastric cancer, and esophageal junction cancer with a HER2 mutation or overexpression, this is the first time fam-trastuzumab deruxtecan-nxki has been approved to treat tumors that express HER2 at low levels. 

Efficacy was demonstrated in the randomized, open-label, multicenter DESTINY-Breast04 clinical trial, in which breast cancer patients with low HER2 expression were randomly assigned to receive either fam-trastuzumab deruxtecan-nxki (373 patients) or chemotherapy (184 patients). 

Patients receiving fam-trastuzumab deruxtecan-nxki had a median progression-free survival of 9.9 months and a median overall survival of 23.4 months, compared with a median progression-free survival of 5.1 months and a median overall survival of 16.8 months among patients receiving chemotherapy.  

In a subset of patients whose tumors also express hormone receptors, those treated with fam-trastuzumab deruxtecan-nxki had a median progression-free survival of 10.1 months and a median overall survival of 23.9 months, compared with a median progression-free survival of 5.4 months and a median overall survival of 17.5 months among patients treated with chemotherapy. 

Breast cancer is the leading cause of cancer death among women in the U.S., with an estimated 287,850 diagnoses and 43,250 deaths anticipated in 2022. Recent studies estimate that 40-60 percent of all breast tumors express low levels of HER2. 

The approval was rendered on August 5, 2022.