CHMP Backs Adjuvant Enhertu in HER2-Positive Early Breast Cancer

AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) has been recommended for approval 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 18 September 2026. The recommendation is a positive opinion from the Committee for Medicinal Products for Human Use (CHMP), which based its decision on results from the DESTINY-Breast05 Phase III trial. In that trial, Enhertu reduced the risk of invasive disease recurrence or death by 53% compared with trastuzumab emtansine (T-DM1), the company reported.

The European Medicines Agency’s meeting highlights confirm that the CHMP adopted the opinion at its 14-17 September 2026 meeting. Enhertu, whose international non-proprietary name is trastuzumab deruxtecan and whose marketing authorisation holder in the EU is Daiichi Sankyo Europe GmbH, was one of 11 medicines to receive positive opinions on extensions of therapeutic indication at the meeting. The committee also recommended 12 new medicines for approval.

According to AstraZeneca, the DESTINY-Breast05 results underpinning the opinion were presented at the 2025 European Society for Medical Oncology Congress and subsequently published in The New England Journal of Medicine.

DESTINY-Breast05 Results and Design

In DESTINY-Breast05, Enhertu significantly reduced the risk of invasive disease recurrence or death, measured as invasive disease-free survival (IDFS), by 53% versus 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), the company reported. At three years, 92.4% of patients in the Enhertu arm were alive and free of invasive disease, compared with 83.7% of those in the T-DM1 arm. AstraZeneca said 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 the efficacy and safety of Enhertu at a dose of 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 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, and other secondary endpoints include overall survival, distant recurrence-free interval, brain metastasis-free interval and safety. The trial enrolled 1,635 patients across Asia, Europe, North America, Oceania and South America.

Susan Galbraith, Executive Vice President of Oncology Haematology R&D at AstraZeneca, said Enhertu “cut the risk of disease recurrence by more than half compared to adjuvant standard of care” for patients with residual disease, adding that the medicine could, if approved, redefine post-surgery care in the EU. John Tsai, Global Head of R&D at Daiichi Sankyo, said patients with HER2-positive early breast cancer who have residual disease after neoadjuvant treatment face a substantially higher risk of recurrence, and said the opinion “underscores the potential role of Enhertu in the curative-intent setting.”

Breast cancer is the most common cancer in women worldwide. Approximately 2.4 million cases were diagnosed in 2024, with more than 690,000 deaths globally, according to World Health Organization figures cited in the announcement; in Europe, approximately 540,000 cases are diagnosed each year, with more than 140,000 deaths. Roughly one in five breast cancers is considered HER2-positive, and about one in three patients with HER2-positive early-stage disease is considered high-risk, meaning a greater likelihood of recurrence and a poor prognosis, the company stated. The current standard of care in the EU’s HER2-positive adjuvant setting for patients with residual invasive disease is T-DM1. Once patients are diagnosed with metastatic disease, the five-year survival rate falls from nearly 100% to approximately 34%, according to National Cancer Institute SEER data referenced in the release.

Existing Approvals and Collaboration

Enhertu is already approved in the US, Brazil, India and Canada for the same adjuvant setting, specifically for adults with HER2-positive breast cancer who have residual invasive disease following neoadjuvant trastuzumab, with or without pertuzumab, and taxane-based treatment, based on DESTINY-Breast05. In the neoadjuvant setting, Enhertu followed by THP is approved in the US, China, India, Singapore, Brazil and Taiwan for adults with HER2-positive Stage II or Stage III breast cancer, based on DESTINY-Breast11; continued approval in China for that use may be contingent on confirmatory trial results. In combination with pertuzumab, the medicine is approved in more than 40 countries and regions as a first-line treatment for unresectable or metastatic HER2-positive breast cancer, based on DESTINY-Breast09.

Beyond those indications, Enhertu is approved in more than 100 countries and regions for previously treated HER2-positive metastatic breast cancer, based on DESTINY-Breast03; in more than 75 for hormone receptor-positive, HER2-low or HER2-ultralow metastatic breast cancer after endocrine therapy, based on DESTINY-Breast06; and in more than 100 for HER2-low metastatic breast cancer after prior systemic therapy, based on DESTINY-Breast04. It is also approved in more than 80 countries and regions for previously treated HER2-mutant metastatic non-small cell lung cancer, in more than 90 for previously treated HER2-positive gastric or gastroesophageal junction adenocarcinoma, and in more than 45 for previously treated HER2-positive solid tumours with no satisfactory alternative treatment options, according to the company.

Enhertu is a HER2-directed antibody drug conjugate built on Daiichi Sankyo’s proprietary DXd ADC technology. It consists of a HER2 monoclonal antibody attached to topoisomerase I inhibitor payloads, an exatecan derivative known as DXd, via tetrapeptide-based cleavable linkers. The medicine was discovered by Daiichi Sankyo and is jointly developed and commercialised by the two companies under a global collaboration entered into in March 2019. Daiichi Sankyo retains exclusive rights to Enhertu in Japan and is responsible for its manufacturing and supply.

The EMA lists the Enhertu extension application as pending a European Commission decision.