AstraZeneca-Daiichi Sankyo Enhertu recommended for approval in EU for patients with HER2-low or HER2-ultralow metastatic breast cancer

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its positive opinion on the results from the DESTINY-Breast06 Phase III trial, which were presented at the 2024 American Society of Clinical Oncology (ASCO) Meeting and published in The New England Journal of Medicine.

In the trial, Enhertu showed a 38% reduction in the risk of disease progression or death versus chemotherapy (hazard ratio [HR] 0.62; confidence interval [CI] 0.52-0.75; p<0.0001) in patients with chemotherapy-naïve HR-positive, HER2-low metastatic breast cancer with a median progression-free survival (PFS) of 13.2 months versus 8.1 months.

In the overall trial population (patients with HER2-low or HER2-ultralow metastatic breast cancer), the median PFS was 13.2 months in patients randomised to Enhertu compared to 8.1 months in those randomised to chemotherapy (HR 0.64; 95% CI 0.54-0.76; p<0.0001). In an exploratory analysis, results were seen to be consistent between patients with HER2-low expression and HER2-ultralow expression.

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said, “Endocrine therapy is typically used in the initial treatment of HR-positive metastatic breast cancer but as the disease progresses the benefit of continued endocrine therapy is limited, and subsequent standard-of-care chemotherapy is associated with poor outcomes. Enhertu has the potential to be the first HER2-directed treatment for patients in the EU with HR-positive, HER2-low or HER2-ultralow metastatic breast cancer directly following endocrine therapy, which would mark an important shift in how patients in this setting are treated.”

Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said, “Enhertu is the first HER2-directed treatment and antibody drug conjugate to show a progression-free survival of more than one year in patients with HER2-low or HER2-ultralow metastatic breast cancer following endocrine therapy. The CHMP recommendation is encouraging and supports our goal of further developing and advancing the way breast cancer is classified and treated.”

HER2 status in the trial was confirmed by a central laboratory and was performed on a tumour sample obtained at the time of initial metastatic diagnosis or later. Approximately 85-90% of patients with HR-positive, HER2-negative metastatic breast cancer were determined to be HER2-low or HER2-ultralow.

The safety profile of Enhertu in DESTINY-Breast06 was consistent with previous clinical trials of Enhertu in breast cancer with no new safety concerns identified.

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.

Enhertu was recently approved in the US for patients with HR-positive, HER2-low or HER2-ultralow metastatic breast cancer that has progressed on one or more endocrine therapies in the metastatic setting. In addition to the EU, regulatory applications are under review in Japan and several other countries based on the DESTINY-Breast06 results.

Enhertu is already approved in more than 75 countries, including the EU, for patients with HER2-low metastatic breast cancer who have received prior chemotherapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.