Site Editor

William J. Gradishar, MD, FACP, FASCO


T-DXd: First Targeted Therapy for HER2-Low Breast Cancer Approved by the FDA

By: JNCCN 360 Staff
Posted: Friday, August 5, 2022

Today, the U.S. Food and Drug Administration (FDA) approved the antibody-drug conjugate fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) for the treatment of patients with unresectable or metastatic HER2-low breast cancer. This is the first approved therapy targeted for patients with the HER2-low breast cancer subtype, which is a newly defined subset of HER2-negative breast cancer. Patients with HER2-low breast cancer are eligible for this targeted therapy if they have received prior chemotherapy in the metastatic setting or had cancer recurrence during, or within 6 months of completing, adjuvant chemotherapy.

This approval is based on the results of DESTINY-Breast04, a randomized, multicenter, open-label clinical trial that enrolled 557 adults with unresectable or metastatic HER2-low breast cancer. The trial included two cohorts: 494 patients with hormone receptor–positive disease and 63 patients with hormone receptor–negative disease. Of these patients, 373 randomly received T-DXd by intravenous infusion every 3 weeks, and 184 randomly received physician’s choice of chemotherapy (eribulin, capecitabine, gemcitabine, nab-paclitaxel, or paclitaxel). The results showed improvement in both progression-free and overall survival in those with unresectable or metastatic HER2-low breast cancer.

The most common adverse reactions in patients receiving T-DXd in DESTINY-Breast04 were nausea, fatigue, alopecia, vomiting, constipation, decreased appetite, musculoskeletal pain, and diarrhea. The prescribing information includes a boxed warning to advise health-care professionals of the risk of interstitial lung disease and embryofetal toxicity. This targeted therapy is not recommended for women who are pregnant.

By continuing to browse this site you permit us and our partners to place identification cookies on your browser and agree to our use of cookies to identify you for marketing. Read our Privacy Policy to learn more.