- First HER2 low metastatic breast cancer phase 3 results for Daiichi Sankyo and AstraZeneca’s ENHERTU offer potential to redefine how the disease is classified and treated
- Plans for global regulatory submissions are underway
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Positive topline results from the pivotal DESTINY-Breast04 phase 3 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, which is the current standard of care. ENHERTU is a HER2 directed antibody drug conjugate (ADC) being jointly developed by Daiichi Sankyo and AstraZeneca.
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 IHC2+ with a negative in-situ hybridization (ISH) score.
HER2 expression is currently defined as either positive or negative.1 HER2 positive cancers are defined as IHC 3+ or IHC 2+/ISH+ and HER2 negative cancers are defined as IHC 0, IHC 1+ or IHC 2+/ISH-.1 Up to 55% of all patients with breast cancer have tumors with a HER2 IHC score of 1+ or a HER2 IHC score of 2+ in combination with a negative ISH test, an expression level not currently eligible for HER2 targeted therapy.2,3 Low HER2 expression occurs in both hormone receptor (HR) positive and HR negative disease.4
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.5 Currently, chemotherapy remains the only treatment option both for patients with HR positive tumors following progression on endocrine (hormone) therapy and for those who are HR negative.6
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 other key secondary endpoints of OS in patients with HR positive disease and 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 continues to redefine the treatment of HER2 targetable cancers. DESTINY-Breast04 is the first ever phase 3 trial of a HER2 directed therapy in patients with HER2 low metastatic breast cancer to show a statistically significant and clinically meaningful benefit in progression-free and overall survival compared to standard treatment,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “We look forward to sharing the detailed findings of DESTINY-Breast04 with the medical community and initiating discussions with regulatory agencies globally with the goal of potentially bringing ENHERTU to patients with metastatic breast cancer previously considered to be HER2 negative.”
“Today’s historic news from DESTINY-Breast04 could reshape how breast cancer is classified and treated,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology R&D, AstraZeneca. “A HER2 directed therapy has never before shown a benefit in patients with HER2 low metastatic breast cancer. These results for ENHERTU are a huge step forward and could potentially expand our ability to target the full spectrum of HER2 expression, validating the need to change the way we categorize and treat breast cancer.”
The data will be presented at an upcoming medical meeting and shared with global health authorities.
Source: ENHERTU(Press release)
