AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) has received expanded approval from the US Food and Drug Administration (FDA) to treat adults with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer.

The treatment is indicated for patients who have previously received chemotherapy in the metastatic setting or recurred during or within six months of receiving adjuvant chemotherapy.

The approval was based on findings from the international, randomised, open-label Phase III DESTINY-Breast04 clinical trial. 

According to the trial data, Enhertu lowered disease progression or mortality risk by 50% compared with chemotherapy according to the physician’s choice in HER2-low metastatic breast cancer patients with hormone receptor (HR)-positive disease or HR-negative disease.

In these subjects, the median progression-free survival (PFS) following Enhertu treatment was 9.9 months compared with 5.1 months for the chemotherapy arm.

Enhertu-treated subjects had a median overall survival (OS) of 23.4 months compared with 16.8 months in the chemotherapy arm, indicating a 36% decline in death risk.

Furthermore, Enhertu’s safety profile was in line with prior clinical trials without any new safety concerns detected.

The latest approval under the Real-Time Oncology Review programme of the FDA comes following previous approval for Enhertu to treat second-line HER2-positive metastatic breast cancer.

With the approval for this indication, AstraZeneca is entitled to make a milestone payment of $200m to Daiichi Sankyo under a partnership deal signed in 2019.

A HER2-directed antibody-drug conjugate (ADC), Enhertu is co-developed and marketed by AstraZeneca and Daiichi Sankyo.

AstraZeneca Oncology Business Unit executive vice-president Dave Fredrickson said: “The rapid approval of Enhertu in HER2-low metastatic breast cancer by the FDA underscores the urgency to bring this transformational medicine to patients as quickly as possible. 

“Patients with HER2-low tumours, who are identified through existing HER2 testing methods, will now have the opportunity to be treated based upon their HER2 status.”

In July, the companies received Priority Review for their supplemental Biologics License Application (BLA) from the US FDA for Enhertu to treat unresectable or metastatic HER2-low breast cancer.