FDA Approves Enhertu for HER2 Low Breast Cancer

This is the first approved therapy targeted to patients with the HER2-low breast cancer subtype. Its approval comes four months ahead of its PDUFA action date.

After a quick review, the FDA has approved Enhertu (fam-trastuzumab-deruxtecan-nxki), an IV infusion for the treatment of patients with unresectable or metastatic HER2-low breast cancer. This is the first approved therapy targeted to patients with the HER2-low breast cancer subtype, which is a newly defined subset of HER2-negative breast cancer.

The agency had accepted the supplemental biologics license application (sBLA) in July 2022, and the company had indicated that the Prescription Drug User Fee Act date (PDUFA) action date was during the fourth quarter of the 2022.

“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,” Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence, said in a press release. “Having therapies that are specially tailored to each patient’s cancer subtype is a priority to ensure access to safe and innovative treatments.”

Related: FDA Accepts sBLA for Enhertu in Low HER2 Breast Cancer

Enhertu is an engineered HER2 directed antibody drug conjugate (ADC) being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca.

About 80% to 85% of those new cases were previously considered to be HER2-negative subtype, which means the tumors do not overexpress, or make too many copies of the HER2 protein. Of that proportion of breast cancer diagnoses, about 60% of patients previously classified as having HER2-negative subtype can now be considered as HER2-low and are now eligible to receive Enhertu. Prior to today’s approval, HER2-low patients received endocrine therapy or chemotherapy.

This approval is based on DESTINY-Breast04, a randomized, multicenter, open label clinical trial that enrolled 557 adult patients with unresectable or metastatic HER2-low breast cancer. The trial included two cohorts: 494 hormone receptor positive patients and 63 hormone receptor negative patients. The results showed improvement in both progression-free survival and overall survival in people with unresectable or metastatic HER2-low breast cancer.