EU Approves Enhertu for Adjuvant HER2-Positive Early Breast Cancer

AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) has been approved in the European Union 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, AstraZeneca announced (AZN ) on 27 October 2026. The European Commission approval triggers a $75 million milestone payment due from AstraZeneca to Daiichi Sankyo for the adjuvant HER2-positive early breast cancer indication, and the company stated the decision is the first EU approval of Enhertu in the curative-intent early breast cancer setting.

The approval by the European Commission is based 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. It follows a positive opinion from the Committee for Medicinal Products for Human Use of the European Medicines Agency, issued on 18 September 2026, which recommended the same indication for approval.

DESTINY-Breast05 Efficacy and Design

In DESTINY-Breast05, Enhertu reduced the risk of invasive disease recurrence or death (invasive disease-free survival, or IDFS) by 53% compared with 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), according to the announcement. Enhertu demonstrated a three-year IDFS rate of 92.4% (95% CI 89.7-94.4), compared with 83.7% for T-DM1 (95% CI 80.2-86.7). The safety profile of Enhertu was consistent with its known profile, with no new safety concerns identified.

DESTINY-Breast05 is a global, multicentre, randomised, open-label Phase III trial evaluating Enhertu at 5.4 mg/kg against T-DM1 in patients with HER2-positive early breast cancer who had residual invasive disease in the breast or axillary lymph nodes following neoadjuvant therapy and a high risk of recurrence. High risk was defined as presentation with inoperable cancer before neoadjuvant therapy or pathologically positive axillary lymph nodes after neoadjuvant therapy. The trial enrolled 1,635 patients across Asia, Europe, North America, Oceania and South America. The primary endpoint is investigator-assessed IDFS, defined as the time from randomisation until the first invasive local, axillary or distant recurrence or death from any cause. The key secondary endpoint is investigator-assessed disease-free survival, with other secondary endpoints including overall survival, distant recurrence-free interval, brain metastases-free interval and safety.

Sibylle Loibl of the German Breast Group and Goethe University Medicine Frankfurt, lead investigator of DESTINY-Breast05, said: “The EU approval of trastuzumab deruxtecan, which demonstrated a more than 50 per cent reduction in risk of recurrence compared to standard of care in DESTINY-Breast05, has the potential to change how we treat eligible patients in this setting.”

Dave Fredrickson, Executive Vice President of AstraZeneca’s Oncology Haematology Business Unit, said the approval “has the potential to establish a new benchmark in this curative-intent setting, with more than 92 per cent of patients alive and free of invasive disease at three years.” Ken Keller, Global Head of Oncology Business and President and CEO of Daiichi Sankyo, Inc., said the decision brings Enhertu into the adjuvant setting, advancing the treatment earlier in the course of disease for patients with HER2-positive early breast cancer, and marks the first approval of Enhertu in early breast cancer in the EU.

According to figures cited in the announcement, breast cancer is the most common cancer in women worldwide, with approximately 2.4 million cases diagnosed in 2024 and more than 690,000 deaths globally; in Europe, approximately 540,000 cases were diagnosed in 2024, with more than 140,000 deaths. Approximately one in five breast cancer cases is considered HER2-positive. HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many tumour types, and HER2 protein overexpression, which may occur as a result of HER2 gene amplification, is often associated with aggressive disease and poor prognosis in breast cancer.

The announcement states that approximately half of patients treated before surgery (39-66%) do not achieve a pathologic complete response, defined as no evidence of invasive cancer cells in the removed breast tissue or lymph nodes following neoadjuvant treatment, increasing their risk of recurrence. Approximately one in four patients with residual disease treated with the historic adjuvant standard of care still experience invasive disease or death, and once disease becomes metastatic, five-year survival falls from around 90% to approximately 30%.

Financial Terms and Existing Approvals

Sales of Enhertu in most EU territories are recognised by Daiichi Sankyo under the collaboration’s financial arrangements. AstraZeneca and Daiichi Sankyo entered a global collaboration to jointly develop and commercialise Enhertu in March 2019 and Datroway (datopotamab deruxtecan) in July 2020, except in Japan, where Daiichi Sankyo maintains exclusive rights for each antibody drug conjugate. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and Datroway.

Enhertu is a HER2-directed DXd antibody drug conjugate discovered by Daiichi Sankyo and jointly developed and commercialised by the two companies. It consists of a HER2 monoclonal antibody attached to topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Enhertu is now approved in more than 35 countries for this adjuvant indication, according to the announcement. The medicine is also approved in more than five countries as a neoadjuvant treatment for adults with HER2-positive Stage II or Stage III breast cancer, in more than 40 countries in combination with pertuzumab as a first-line treatment for unresectable or metastatic HER2-positive breast cancer, and in more than 100 countries for previously treated unresectable or metastatic HER2-positive disease. Additional approvals cover HER2-low and HER2-ultralow metastatic breast cancer, HER2-mutant non-small cell lung cancer, HER2-positive gastric or gastroesophageal junction adenocarcinoma, and HER2-positive solid tumours.