CHMP Backs Enhertu as Adjuvant Therapy for HER2-Positive Breast Cancer With Residual Disease
核心洞察
The EMA's CHMP has recommended EU approval of Enhertu as monotherapy for adults with resected HER2-positive breast cancer (搜索) who have residual invasive disease after neoadjuvant therapy.
The opinion rests on DESTINY-Breast05, in which Enhertu cut the risk of invasive disease recurrence or death by 53% versus T-DM1 (HR 0.47; 95% CI 0.34-0.66; p<0.0001).
At three years, 92.4% of patients on Enhertu were alive and free of invasive disease versus 83.7% on T-DM1, with no new safety concerns reported.
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (搜索) has recommended approval of Enhertu (trastuzumab deruxtecan) in the European Union as a monotherapy for the adjuvant treatment of adults with resected HER2-positive breast cancer (搜索) who have residual invasive disease after neoadjuvant taxane-based and HER2 (搜索)-targeted treatment. The recommendation will now be reviewed by the European Commission, which holds the authority to grant marketing authorisations in the EU.
The positive opinion 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. Enhertu is a HER2 (搜索)-directed DXd antibody drug conjugate discovered by Daiichi Sankyo and jointly developed and commercialised with AstraZeneca.
DESTINY-Breast05 Efficacy
In the trial, Enhertu significantly reduced the risk of invasive disease recurrence or death, the invasive disease-free survival (IDFS) endpoint, by 53% compared with trastuzumab emtansine (T-DM1) in patients with HER2-positive breast cancer (搜索) and residual invasive disease following neoadjuvant therapy. The hazard ratio was 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 (95% CI 89.7-94.4), compared with 83.7% in the T-DM1 arm (95% CI 80.2-86.7). Enhertu also significantly reduced the risk of disease recurrence or death, the disease-free survival (DFS) endpoint, by 53% versus T-DM1 (HR 0.47; 95% CI 0.34-0.66; p<0.0001), with three-year DFS rates of 92.3% (95% CI 89.5-94.3) and 83.5% (95% CI 79.9-86.4), respectively.
DESTINY-Breast05 is a global, multicentre, randomised, open-label Phase III trial evaluating Enhertu at 5.4 mg/kg versus T-DM1 in patients with HER2 (搜索)-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 was defined as presentation with inoperable cancer prior to 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 time from randomisation to 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.
Safety Profile
The safety profile of Enhertu in DESTINY-Breast05 was consistent with its known profile, with no new safety concerns identified. The most common treatment-related adverse events were nausea (71.3%), constipation (32.0%), decreased neutrophil count (31.6%) and vomiting (31.0%). Interstitial lung disease or pneumonitis occurred in 9.6% of patients treated with Enhertu, as determined by an independent adjudication committee. Most of these events were low grade: grade 1 in 16 patients (2.0%) and grade 2 in 52 patients (6.5%). Two grade 5 events of interstitial lung disease or pneumonitis (0.2%) occurred in the Enhertu arm.
Clinical Rationale
Approximately one in three patients with HER2 (搜索)-positive early-stage breast cancer is considered high risk, meaning they are more likely to experience recurrence and have a poor prognosis. The current standard of care in the HER2-positive adjuvant setting for patients with residual invasive disease in the EU is T-DM1. Despite additional treatment with the current standard of care for residual disease, some patients still experience invasive disease or death. Once patients are diagnosed with metastatic disease, the five-year survival rate falls from nearly 100% to approximately 34%.
"Patients with HER2 (搜索)-positive early breast cancer who have residual disease after neoadjuvant treatment experience a substantially higher risk of recurrence, making effective adjuvant treatment especially important," said John Tsai, Global Head, R&D, Daiichi Sankyo. "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."
Susan Galbraith, Executive Vice President, Oncology Haematology R&D at AstraZeneca, said: "This positive CHMP opinion marks a significant step towards bringing Enhertu into early-stage HER2-positive breast cancer (搜索) 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."
Regulatory and Development Status
Enhertu is already approved in the US, Brazil, Canada and India for the adjuvant treatment of adults with HER2-positive breast cancer (搜索) who have residual invasive disease following neoadjuvant trastuzumab, with or without pertuzumab, and taxane-based treatment, based on DESTINY-Breast05.
Enhertu consists of a HER2 (搜索) monoclonal antibody attached to topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. It is the lead ADC in Daiichi Sankyo's oncology portfolio and the most advanced programme in AstraZeneca's ADC scientific platform. The two companies entered a global collaboration to jointly develop and commercialise Enhertu in March 2019, with Daiichi Sankyo responsible for manufacturing and supply.
Breast cancer is the most common cancer in women worldwide and the leading cause of cancer-related death among women. Approximately 2.4 million breast cancer cases were diagnosed in 2024, with more than 690,000 deaths globally. In Europe, approximately 540,000 cases are diagnosed annually, with more than 140,000 deaths. Approximately one in five cases of breast cancer is considered HER2 (搜索)-positive.