AstraZeneca and Daiichi Sankyo's Enhertu (trastuzumab deruxtecan) in combination with pertuzumab has been recommended for approval in the European Union (EU) for the 1st-line treatment of adult patients with unresectable or metastatic HER2-positive breast cancer.
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its positive opinion on results from the DESTINY-Breast09 Phase III trial presented at the 2025 American Society of Clinical Oncology Annual Meeting and subsequently published in The New England Journal of Medicine.1
Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "HER2-positive metastatic breast cancer is an aggressive subtype, so starting patients on an effective HER2-targeted treatment early and continuing it for as long as they benefit can have a meaningful impact on long-term outcomes. DESTINY-Breast09 sets a new benchmark with a median progression-free survival of more than three years, underscoring the potential of Enhertu plus pertuzumab to redefine first-line treatment for patients with HER2-positive metastatic breast cancer."
John Tsai, Global Head, R&D, Daiichi Sankyo, said: "Enhertu in combination with pertuzumab improved progression-free survival by more than one year compared with the current first-line standard of care, representing a meaningful advantage early in the treatment of patients with metastatic HER2-positive disease. Today's positive CHMP opinion brings us closer to making Enhertu available in the EU as a first-line treatment option for eligible patients with HER2-positive metastatic breast cancer, marking an important milestone in moving this medicine earlier in the treatment pathway."
In DESTINY-Breast09, Enhertu in combination with pertuzumab reduced the risk of disease progression or death by 44% versus a taxane, trastuzumab and pertuzumab (THP) (based on a hazard ratio of 0.56; 95% confidence interval [CI]: 0.44-0.71; p<0.00001) in patients with HER2-positive metastatic breast cancer who had not received prior chemotherapy or HER2-targeted therapy or had received neoadjuvant or adjuvant HER2-targeted therapy more than six months before the diagnosis of advanced or metastatic disease. Median progression-free survival (PFS) was 40.7 months with Enhertu in combination with pertuzumab compared to 26.9 months with THP. The PFS benefit was consistent across subgroups, including for the prespecified stratification factors of hormone receptor status, de novo or recurrent disease and PIK3CA mutation status.
The safety profile of Enhertu plus pertuzumab was consistent with the known profiles of each individual therapy with no new safety concerns identified.
Enhertu in combination with pertuzumab is approved in the US, Switzerland and other countries as a 1st-line treatment for patients with metastatic HER2-positive breast cancer based on the results from the DESTINY-Breast09 trial.
Enhertu is also under review in the EU for patients with HER2-positive breast cancer who have residual invasive disease after neoadjuvant HER2-targeted treatment based on data from the DESTINY-Breast05 trial.
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 metastatic 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 While survival rates are high for those diagnosed with early breast cancer, only about 30% of patients diagnosed with or whose disease has progressed to metastatic disease are expected to live five years following diagnosis.4
HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours including breast cancer.5 HER2 protein overexpression may occur as a result of HER2 gene amplification.4 Approximately one in five cases of breast cancer is considered HER2-positive.5
HER2-positive metastatic breast cancer is an aggressive disease driven by overexpression or amplification of HER2 that affects 15% to 20% of patients with metastatic breast cancer.6 While HER2-targeted therapies have improved outcomes, prognosis remains poor with most patients experiencing disease progression within two years of first-line treatment with THP, which has been the standard of care for more than a decade.6-8 Further, approximately one in three patients do not receive any treatment following first-line therapy due to disease progression or death.10,11
DESTINY-Breast09
DESTINY-Breast09 is a global, multicentre, randomised, open-label, Phase III trial evaluating the efficacy and safety of Enhertu (5.4 mg/kg) either alone or in combination with pertuzumab versus standard of care THP as first-line treatment in patients with HER2-positive metastatic breast cancer who had not received prior chemotherapy or HER2-targeted therapy or had received neoadjuvant or adjuvant HER2-targeted therapy more than six months before the diagnosis of advanced or metastatic disease.
Patients were randomised 1:1:1 to receive either Enhertu monotherapy with a pertuzumab matching placebo; Enhertu in combination with pertuzumab; or THP. Randomisation was stratified by prior treatment (de novo metastatic disease versus progression from early-stage disease), hormone receptor (HR) status and PIK3CA mutation status.
The primary endpoint of DESTINY-Breast09 is PFS as assessed by BICR in both the Enhertu monotherapy and Enhertu combination arms. Secondary endpoints include investigator-assessed PFS, overall survival, ORR, duration of response, pharmacokinetics and safety. The investigational arm assessing Enhertu monotherapy versus THP remains blinded to patients and investigators and will continue to the final PFS analysis.
