Enhertu Gains EMA’s CHMP Support for HER2-Low Metastatic Breast Cancer Treatment

The European Medicines Agency (EMA) committee (CHMP) has recommended approving trastuzumab deruxtecan (Enhertu), a HER2-directed antibody-drug conjugate for certain patients with metastatic breast cancer. Phase III DESTINY-Breast06 trial data showed a median progression-free survival of 13.2 months versus 8.1 for chemotherapy, marking a significant shift in treatment options for these patients. Regulatory approval decision awaits.

The drug, jointly developed by AstraZeneca and Daiichi Sankyo, would be used as a monotherapy in adults who have hormone receptor (HR)-positive, HER2-low or HER2-ultralow breast cancer following at least one course of endocrine therapy in the metastatic setting.

Ken Takeshita, Global Head of R&D at Daiichi Sankyo, added: “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.”

Positive Results in DESTINY-Breast06

The EMA’s Committee for Medicinal Products for Human Use (CHMP) based its recommendation on data from the DESTINY-Breast06 Phase III trial. Presented at the 2024 ASCO and published in NEJM, the study found that Enhertu significantly outperformed chemotherapy in patients who had not previously received chemotherapy for advanced disease.

• Median Progression-Free Survival (PFS): 13.2 months (Enhertu) vs. 8.1 months (chemotherapy)
• Risk Reduction: Enhertu lowered the risk of disease progression or death by 38% compared to chemotherapy (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.52-0.75; p<0.0001).

In the broader group—including both HER2-low and HER2-ultralow patients—Enhertu achieved a median PFS of 13.2 months, compared to 8.1 months with chemotherapy (HR 0.64; 95% CI 0.54-0.76; p<0.0001). Exploratory analyses indicated consistent benefits between the two subgroups (HER2-low and HER2-ultralow).

A Potential Shift in Treatment

For patients with HR-positive breast cancer, endocrine therapy is often used first. However, once resistance develops, treatment options typically turn to chemotherapy, which can be less effective and lead to undesirable side effects.

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.”

About the Drug and Its Safety Profile

Enhertu is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) that merges a HER2-targeting monoclonal antibody with a potent chemotherapy payload, designed to deliver the cancer-fighting agent directly to tumour cells. In the DESTINY-Breast06 trial, the safety profile of Enhertu appeared consistent with previous studies, and no new safety concerns emerged.

Already approved in more than 75 countries for certain types of breast cancer, Enhertu recently gained authorisation in the United States for HR-positive, HER2-low or HER2-ultralow metastatic breast cancer after progression on at least one endocrine therapy. Additional regulatory applications are under review in Japan and other nations.

Next Steps

With the positive opinion from the CHMP, the European Commission will now consider granting approval for Enhertu in the EU. If confirmed, this recommendation may alter the treatment paradigm for patients with HR-positive, HER2-low or HER2-ultralow metastatic breast cancer who have already undergone at least one course of endocrine therapy.