NEW YORK – AstraZeneca on Friday said the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) recommended the HER2-targeted antibody-drug conjugate Enhertu (trastuzumab deruxtecan) as a treatment for patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-low or HER2-ultralow breast cancer who have received at least one endocrine therapy in the metastatic setting and are not candidates for endocrine therapy as the next line of treatment.
The committee based its opinion on results from the Phase III DESTINY-Breast06 trial in which patients with HER2-low disease on Enhertu had a 38 percent reduced risk of disease progression or death compared to those on chemotherapy. Median progression-free survival in this cohort was 13.2 months for those on Enhertu versus 8.1 months for chemotherapy. In the overall cohort, which included both HER2-low and HER2-ultralow patients, the results were consistent with a 13.2-month median progression-free survival for patients on Enhertu compared to 8.1 months for those on chemotherapy.
"Enhertu has the potential to be the first HER2-directed treatment for patients in the [European Union] with HR-positive, HER2-low or HER2-ultralow metastatic breast cancer directly following endocrine therapy, which would mark an important shift in how patients in this setting are treated," Susan Galbraith, executive VP of oncology hematology R&D at AstraZeneca, said in a statement.
For this new indication, HER2-low is defined as having an immunohistochemistry (IHC) result of 1+ or 2+ with a negative in situ hybridization test, while HER2-ultralow is defined as IHC 0 with membrane staining. Some pathologists have questioned the reliability of IHC testing for capturing very low levels of HER2 expression, and clinical guidelines have not yet fully incorporated the new categories.
AstraZeneca is developing and commercializing Enhertu jointly with Daiichi Sankyo, which originally discovered the drug. In January, the US Food and Drug Administration approved Enhertu in the HER2-low and -ultralow metastatic breast cancer setting, and it is under review in Japan and several other countries based on results from DESTINY-Breast06.