The first HER2-low metastatic breast cancer Phase III results for AstraZeneca and Daiichi Sankyo’s Enhertu offer potential to redefine how the disease is classified and treated, said the two companies, in a statement.
Positive high-level results from the pivotal DESTINY-Breast04 Phase III trial showed Enhertu (trastuzumab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement in both progression-free survival (PFS) and overall survival (OS) in patients with HER2-low unresectable and/or metastatic breast cancer, regardless of hormone receptor (HR) status versus physician’s choice of chemotherapy.
The HER2-directed antibody drug conjugate (ADC) is being jointly developed by AstraZeneca and Daiichi Sankyo.
All patients in the trial received a HER2 test, and the results were centrally confirmed. HER2-low status was defined as an immunohistochemistry (IHC) score of 1+ or IHC 2+ with a negative in-situ hybridisation (ISH) score.
Up to 55% of all patients with breast cancer have tumours with a HER2 IHC score of 1+, or 2+ in combination with a negative ISH test, a level of HER2 expression not currently eligible for HER2-targeted therapy. HER2-low expression occurs in both HR-positive and HR-negative disease.
HER2 testing is well established to determine an appropriate treatment strategy in metastatic breast cancer. Targeting the lower range of HER2 expression may offer another approach to delay disease progression and extend survival in patients with metastatic breast cancer. Currently, chemotherapy remains the only treatment option both for patients with HR-positive tumours following progression on endocrine (hormone) therapy, and for those who are HR-negative.
DESTINY-Breast04 met its primary endpoint, where Enhertu demonstrated superior PFS in previously treated patients with HR-positive HER2-low metastatic breast cancer compared to the standard-of-care chemotherapy. The trial met the key secondary endpoint of PFS in patients with HER2-low metastatic breast cancer regardless of HR status (HR-positive or HR-negative). The trial also met the key secondary endpoints of OS in patients with HR-positive disease and in patients regardless of HR status at interim analysis.
The safety profile of Enhertu was consistent with previous clinical trials, with no new safety concerns identified. Overall interstitial lung disease (ILD) rates were consistent with that observed in late-line HER2-positive breast cancer trials of Enhertu, with a lower rate of Grade 5 ILD observed as determined by an independent adjudication committee.
Enhertu (5.4mg/kg) is approved in more than 40 countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens based on the results from the DESTINY-Breast01 trial. The drug is being further assessed in a comprehensive clinical development programme evaluating efficacy and safety across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers.
The data from the trial will be presented at a forthcoming medical meeting and shared with global health authorities, said AstraZeneca.
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