Full Approval for a HER2-targeting Therapy 

The FDA has granted full approval to an antibody-drug conjugate for certain patients with breast cancer. 

The U.S. Food and Drug Administration (FDA) has approved fam-trastuzumab deruxtecan-nxki (Enhertu) for the treatment of certain adult patients with HER2-positive breast cancer. Patients are eligible if their tumor is metastatic or unable to be surgically removed, and if they have experienced a relapse within six months of completion of another HER2-targeting therapy. 

Fam-trastuzumab deruxtecan-nxki is an antibody-drug conjugate—a type of therapeutic in which a toxic drug is attached to an antibody that targets the drug to the surface of cancer cells. When the target protein is pulled inside the cell to be recycled, the toxic drug enters as well and kills the cell. In fam-trastuzumab deruxtecan-nxki, the antibody trastuzumab targets the HER2 receptor, which is overexpressed in many breast cancers. The toxic payload deruxtecan inhibits the enzyme topoisomerase, which is crucial for DNA replication. 

Fam-trastuzumab deruxtecan-nxki was granted accelerated approval for this patient population on December 20, 2019. To achieve full approval, researchers performed a multicenter, randomized, open-label clinical trial that randomly assigned 524 patients to receive either fam-trastuzumab deruxtecan-nxki or another HER2-targeting antibody-drug conjugate, ado-trastuzumab emtansine (Kadcyla). 

Patients receiving fam-trastuzumab deruxtecan-nxki had not yet reached the median progression-free survival, whereas patients receiving ado-trastuzumab emtansine had a median progression-free survival of 6.8 months. Further, the overall response rate was 82.7 percent among patients treated with fam-trastuzumab deruxtecan-nxki compared with 36.1 percent among patients treated with ado-trastuzumab emtansine. 

Data from this trial were presented at the 2021 San Antonio Breast Cancer Symposium (SABCS), hosted by UT Health San Antonio and the American Association for Cancer Research (AACR). 

Breast cancer is the leading cause of cancer death in women. According to federal statistics, nearly 290,000 women are predicted to be diagnosed with breast cancer in 2022, and more than 43,000 women are predicted to die of the disease. 

The FDA decision was rendered on May 4, 2022.