AstraZeneca (AZ) and Daiichi Sankyo have shared positive results from a late-stage study of their HER2-directed antibody drug conjugate Enhertu (trastuzumab deruxtecan) in a subset of breast cancer patients.
The phase 3 DESTINY-Breast06 has been comparing the drug against chemotherapy in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-low or HER2-ultralow advanced or metastatic breast cancer.
Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths globally, with more than two million cases of the disease diagnosed in 2022.
HR-positive, HER2-negative is the most common breast cancer subtype, with up to 65% of these cases estimated to be HER2-low and an additional 25% may be HER2-ultralow.
There were no targeted therapies specifically approved for patients with HER2-low expression prior to the approval of Enhertu in HER2-low metastatic breast cancer last year, and there are still no targeted therapies specifically authorised for those with HER2-ultralow expression.
Results from DESTINY-Breast06 demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to chemotherapy in the primary trial population of patients with HR-positive, HER2-low metastatic breast cancer following one or more lines of endocrine therapy.
A statistically significant and clinically meaningful improvement in PFS was observed in the overall trial population, and a prespecified subgroup analysis showed the clinically meaningful improvement was consistent between patients with HER2-low and HER2-ultralow expression.
Enhertu also demonstrated an early trend towards overall survival (OS) improvement versus chemotherapy in patients with HER2-low metastatic breast cancer and in the overall trial population, but this data was not mature at the time of analysis and the trial will continue to further assess OS and other secondary endpoints.
Susan Galbraith, executive vice president, oncology research and development, AZ, said: “DESTINY-Breast06 shows that Enhertu could become a new standard of care for patients with HER2-low and HER2-ultralow metastatic breast cancer following one or more lines of endocrine therapy.
“This data underscores the potential for treatment with Enhertu across the spectrum of HR-positive breast cancer, further redefining the treatment of metastatic breast cancer.”