Enhertu approved in the EU as the first HER2-directed therapy for patients with HER2-low metastatic breast cancer

Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use and is based on results from the DESTINY-Breast04 Phase III trial, which were presented at the American Society of Clinical Oncology 2022 Annual Meeting and published in The New England Journal of Medicine.(previously cited).

Breast cancer and HER2 expression; Breast cancer is the most common cancer and is one of the leading causes of cancer-related deaths worldwide. More than two million patients with breast cancer were diagnosed in 2020 with nearly 685,000 deaths globally. In Europe, approximately 531,000 breast cancer patients are diagnosed annually with around 141,000 deaths.

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours including breast, gastric, lung and colorectal cancers, and is one of many biomarkers expressed in breast cancer tumour. HER2 expression is determined by an immunohistochemistry (IHC) test which estimates the amount of HER2 protein on a cancer cell, and/or an in situ hybridisation (ISH) test, which counts the copies of the HER2 gene in cancer cells. HER2 tests provide IHC and ISH scores across the full HER2 spectrum and are routinely used to determine appropriate treatment options for patients with metastatic breast cancer.

HER2-positive cancers are currently defined as HER2 expression measured as IHC 3+ or IHC 2+/ISH+, and HER2-negative cancers are defined as HER2 expression measured as IHC 0, IHC 1+ or IHC 2+/ISH-. However, approximately half of all breast cancers are HER2-low, defined as a HER2 score of IHC1+ or IHC 2+/ISH-.HER2-low occurs in both HR-positive and HR-negative disease.

Historically, patients with HR-positive metastatic breast cancer and HER2-low disease have had limited effective treatment options following progression on endocrine (hormone) therapy. Additionally, few targeted options are available for those with HR-negative disease.