FDA Approves First Therapy for New HER2-low Breast Cancer Subtype


The FDA approved a new drug that treats unresectable and metastatic HER2-low breast cancer, giving patients with this new subtype a treatment beyond chemotherapy.

Today, the FDA approved fam-trastuzumab-deruxtecan-nxki (Enhertu; Daiichi Sankyo, Inc), which is the first HER2-low breast cancer treatment.

“Today’s approval highlights the FDA’s commitment to be at the forefront of scientific advances, making targeted cancer treatment options available for more patients,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, in a press release.

In the United States, about 80% to 85% of the estimated 287,850 new cases of female breast cancer in 2022 would have been diagnosed as HER2-negative subtypes, which include hormone receptor positive and triple negative breast cancer. However, with the new approval, 60% of patients will be reconsidered as having the HER2-low subtype.

HER2-low is a subtype of HER2 breast cancer. The HER2 receptors (made by the HER2 gene) are expressed differently in HER2-negative and HER2-low. HER2-negative is comprised of hormone receptor positive and triple negative breast cancer. Both types of cancer can determine the type of treatment that the patient receives.

Researchers pulled together 557 participants with unresectable or metastatic HER2-low breast cancer. Patients ranged in age from 28 to 81 years old. The median age was age 57 years, and almost 25% of patients were age 65 years or older. Race was reported as 48% White, 40% Asian, 2% Black, and 3.8% Hispanic/Latino participants. Further, of those included in the analysis, participants either had unresectable tumors or metastatic HER2-low breast cancer.

Researchers investigated fam-trastuzumab-deruxtecan-nxki in the DESTINY-Breast04 trial, which was randomized, multicenter, and an open label clinical trial that included 557 patients. Of the total trial participants, 494 were hormone receptor positive (HR+) and 63 were hormone receptor negative (HR-).

In 373 participants, researchers randomized the administration of intravenous infusion of fam-trastuzumab-deruxtecan-nxki every 3 weeks. For the remaining 184 participants, researchers gave them the chemotherapy recommended by their health care provider. As a result, fam-trastuzumab-deruxtecan-nxki improved the overall survival of unresectable or metastatic HER2-low breast cancer patients.

Granted priority review, the rapid FDA approval aligns with President Biden’s Cancer Moonshot program goals. Cancer Moonshot aims to reduce cancer death rates and help patients and families by advancing cancer research and technology. This includes individualizing treatments for new cancer variations like HER2-low.

The administration of fam-trastuzumab-deruxtecan-nxki caused adverse events including nausea, fatigue, alopecia, vomiting, constipation, decreased appetite, musculoskeletal pain, and diarrhea in some patients. Other risks include interstitial lung disease and embryo-fetal toxicity, so it is not recommended for women who are pregnant.

HER2-low patients can get fam-trastuzumab-deruxtecan-nxki if they have recurrent cancer within 6 months of adjuvant chemotherapy, or if they received chemotherapy for a metastatic case.

This approval was given priority 4 months before the deadline of the Prescription Drug User Fee Act.

“Having therapies that are specially tailored to each patient’s cancer subtype is a priority to ensure access to safe and innovative treatments,” Pazdur said in a press release.


FDA. FDA Approves First Targeted Therapy for HER2-Low Breast Cancer. FDA website. Aug 5, 2022. Accessed on Aug 5, 2022.

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