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.

U.S. Food and Drug Administration

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