AstraZeneca (AZ) and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) has been approved by the US Food and Drug Administration (FDA) to treat adults with unresectable or metastatic breast cancer expressing low levels of HER2, a newly defined subset of HER2-negative breast cancer.
The decision, which comes four months ahead of schedule, was based on results from the DESTINY-Breast04 phase 3 trial, in which Enhertu reduced the risk of disease progression or death by 50% and increased overall survival by more than six months versus chemotherapy.
HER2 receptors, which are proteins made by the HER2 gene, are important in determining a patient’s treatment. HER2-low tumours are defined as those whose cells contain lower levels of the HER2 protein on their surface.
According to the National Cancer Institute, an estimated 287,850 new cases of female breast cancer will be diagnosed in 2022 in the US. Approximately 80-85% of those new cases were previously considered to be HER2-negative subtype, meaning the tumours do not overexpose, or make too many copies of the HER2 protein. However, of that proportion, around 60% of patients can now be considered as HER2-low.
Enhertu belongs to a class of therapies called antibody drug conjugates (ADC), and consists of a HER2 monoclonal antibody chemically linked to a cell-killing chemotherapy drug.
Patients with HER2-low breast cancer are eligible for Enhertu if they have received a prior chemotherapy in the metastatic setting, or if their cancer returned during, or within six months of completing, adjuvant chemotherapy, the FDA stated.
The regulator also stated that the drug should carry a boxed warning to highlight the risk of a type of lung scarring and foetal toxicity, adding that the therapy is not recommended for pregnant women.
Regulatory applications for Enhertu are also currently under review in Europe, Japan and several other countries based on the DESTINY-Breast04 results.
Commenting on the approval, Shanu Modi, medical oncologist, Memorial Sloan Kettering Cancer Center, said: “Approximately half of all patients with breast cancer have tumours that are HER2-low, which have previously been classified as HER2-negative and have not had effective treatment options with HER2-targeted medicines.
“Based on the promising results of the DESTINY-Breast04 trial, clinicians are starting to differentiate levels of HER2 expression and redefine how metastatic breast cancer is classified with a distinct HER2-low patient population that may be eligible for [Enhertu].”