ENHERTU® Type II Variation Application Validated in the EU as Post-Neoadjuvant Treatment for Patients with HER2 Positive Early Breast Cancer
The European Medicines Agency (EMA) has validated the Type II Variation marketing authorization application for ENHERTU® (trastuzumab deruxtecan) as a monotherapy for adult patients with HER2 positive (immunohistochemistry [IHC] 3+ or in-situ hybridization [ISH]+) breast cancer who have residual invasive disease after neoadjuvant HER2 targeted treatment.
ENHERTU is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/NYSE: AZN).
The validation confirms the completion of the application and commences the scientific review process by the EMA’s Committee for Medicinal Products for Human Use (CHMP). The application is based on data from the DESTINY-Breast05 phase 3 trial presented at the 2025 European Society for Medical Oncology (#ESMO25) Congress and subsequently published in The New England Journal of Medicine. In the trial, ENHERTU demonstrated a statistically significant and clinically meaningful improvement in invasive disease-free survival (IDFS) versus trastuzumab emtansine (T-DM1) in patients with HER2 positive breast cancer with residual invasive disease following neoadjuvant therapy.
“Patients who have residual invasive disease despite neoadjuvant therapy face a heightened risk of recurrence and are in need of better options following neoadjuvant treatment and surgery,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “This validation in the EU is an important step toward bringing ENHERTU to eligible patients earlier in the treatment journey to help reduce the risk of disease recurrence and progression to metastatic disease.”
About DESTINY-Breast05
DESTINY-Breast05 is a global, multicenter, randomized, open-label, phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) versus T-DM1 in patients with HER2 positive early breast cancer with residual invasive disease in breast or axillary lymph nodes following neoadjuvant therapy and a high risk of recurrence. High risk of recurrence was defined as presentation with inoperable cancer (prior to neoadjuvant therapy) or pathologically positive axillary lymph nodes following neoadjuvant therapy.
The primary endpoint of DESTINY-Breast05 is investigator-assessed IDFS, which is defined as the time from randomization until first invasive local, axillary or distant recurrence or death from any cause. The key secondary endpoint is investigator-assessed disease-free survival. Other secondary endpoints include overall survival, distant recurrence-free interval, brain metastases-free interval and safety.
About Post Neoadjuvant Treatment for HER2 Positive Early Breast Cancer
Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.1 More than two million breast cancer cases were diagnosed in 2022, with more than 665,000 deaths globally.1 In Europe, approximately 557,000 cases of breast cancer are diagnosed annually, with more than 144,000 deaths.1
HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors including breast cancer.2 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer.2 Approximately one in five cases of breast cancer is considered HER2 positive.3
For patients with HER2 positive early breast cancer, achieving pathologic complete response (pCR) with neoadjuvant treatment is the earliest indicator of improved long-term survival.4 However, approximately half of patients who receive neoadjuvant treatment do not experience pCR, putting them at increased risk of disease recurrence.5,6,7,8,9
Despite receiving additional treatment for residual disease in the post-neoadjuvant setting, some patients still experience invasive disease or death and current treatment options have shown limited impact on central nervous system recurrence.10 Once patients are diagnosed with metastatic disease, the five-year survival rate drops from nearly 90% to approximately 30%.11
Post-neoadjuvant therapy represents a key opportunity to minimize the risk of recurrence and prevent progression to metastatic disease for patients with residual disease. New treatment options are needed in the early breast cancer setting to help reduce the likelihood of disease progression and improve long-term outcomes for more patients.12,13
About ENHERTU
ENHERTU (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, ENHERTU is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.
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