AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) has been recommended for approval in the European Union (EU) as a monotherapy for the adjuvant treatment of adult patients with resected HER2-positive breast cancer who have residual invasive disease after neoadjuvant taxane-based and HER2-targeted treatment.
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency based its positive opinion on results from the DESTINY-Breast05 Phase III trial presented at the 2025 European Society for Medical Oncology Congress and subsequently published in The New England Journal of Medicine.1
Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “This positive CHMP opinion marks a significant step towards bringing Enhertu into early-stage HER2-positive breast cancer in the EU. Enhertu cut the risk of disease recurrence by more than half compared to adjuvant standard of care for patients with residual disease, and if approved could redefine post-surgery care in the EU, keeping patients disease-free for longer and increasing the potential for cure.”
John Tsai, Global Head, R&D, Daiichi Sankyo, said: “Patients with HER2-positive early breast cancer who have residual disease after neoadjuvant treatment experience a substantially higher risk of recurrence, making effective adjuvant treatment especially important. This positive CHMP opinion underscores the potential role of Enhertu in the curative-intent setting where it is critical to maximise the potential for sustained long-term outcomes.”
In DESTINY-Breast05, Enhertu significantly reduced the risk of invasive disease recurrence or death (invasive disease-free survival [IDFS]) by 53% compared to trastuzumab emtansine (T-DM1) in patients with HER2-positive breast cancer with residual invasive disease following neoadjuvant therapy (based on a hazard ratio of 0.47; 95% confidence interval 0.34-0.66, p<0.0001). At three years, 92.4% of patients in the Enhertu arm were alive and free of invasive disease, compared to 83.7% of those in the T-DM1 arm.
The safety profile of Enhertu was consistent with its known profile with no new safety concerns identified.
Enhertu is approved in the US and other countries for the adjuvant treatment of patients with HER2-positive breast cancer who have residual invasive disease following neoadjuvant treatment based on DESTINY-Breast05.
Enhertu is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.
Notes
HER2-positive early breast cancer
Breast cancer is the most common cancer in women worldwide and the leading cause of cancer-related death among women.2 Approximately 2.4 million breast cancer cases were diagnosed in 2024, with more than 690,000 deaths globally.2 In Europe, approximately 540,000 cases of breast cancer are diagnosed annually, with more than 140,000 deaths.3
HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours, including breast cancer.4 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.4 Approximately one in five cases of breast cancer is considered HER2-positive.5
Approximately one in three patients with HER2-positive early-stage breast cancer is considered high-risk, meaning they are more likely to experience disease recurrence and have a poor prognosis.6 The current standard of care in the HER2-positive adjuvant setting (after surgery) for patients with residual invasive disease in the EU is TDM-1.7
Despite receiving additional treatment with current standard of care for residual disease, some patients still experience invasive disease or death.8 Once patients are diagnosed with metastatic disease, the five-year survival rate drops from nearly 100% to approximately 34%.9
Adjuvant therapy represents a key opportunity to minimise the risk of recurrence and prevent progression to metastatic disease for patients with residual disease.8,10,11 New treatment options are needed in the early breast cancer setting to improve long-term outcomes for more patients.
DESTINY-Breast05
DESTINY-Breast05 is a global, multicentre, randomised, open-label, Phase III trial evaluating the efficacy and safety of Enhertu (5.4mg/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 randomisation until first invasive local, axillary or distant recurrence or death from any cause. The key secondary endpoint is investigator-assessed DFS. Other secondary endpoints include overall survival, distant recurrence-free interval, brain metastasis-free interval and safety.
