Clinical study confirms that ADC drug can effectively treat brain metastases from breast cancer

The term "pink killer" refers to breast cancer, whose prevalence rate has long ranked first among female malignant tumors. Breast cancer has surpassed lung cancer as the most common cancer worldwide, according to data from the International Agency for Research on Cancer (IARC) on the global burden of cancer in 2020.

Breast cancer is prone to metastases. Not only that, many breast cancer patients are insensitive to chemotherapy, targeted therapy, and immunotherapy, which greatly affects the patient's treatment prognosis.

On August 8, 2022, researchers from the Medical University of Vienna published a research paper entitled: Trastuzumab deruxtecan in HER2-positive breast cancer with brain metastases: a single-arm, phase 2 trial in the top international medical journal Nature Medicine. This phase 2 clinical trial confirmed that the HER2-targeting antibody-drug conjugate (ADC) drug Trastuzumab deruxtecan can effectively treat and even clear brain metastases in patients with HER2-positive breast cancer, opening up a new route for oncology research and targeted therapy, which is also a pioneering study in the treatment of cancer brain metastases.

Trastuzumab deruxtecan, trade name Enhertu®, or T-DXd for short. It is an ADC drug jointly developed by AstraZeneca and Daiichi Sankyo, which was approved by the FDA in 2019 for the treatment of patients with unresectable or metastatic HER2-positive breast cancer. It combines the HER2 monoclonal antibody Trastuzumab with the topoisomerase 1 inhibitor exatecan derivative (DXd), thereby blocking the HER2 protein while releasing a chemical toxin for anti-cancer effect.

15 patients (14 women and 1 man) with HER2-positive breast cancer and brain metastases participated in this clinical trial, with Trastuzumab deruxtecan used as treatment.

Male breast cancer accounts for less than 1% of all cases. Additionally, 15% of breast cancers are HER2-positive breast cancers, which are more likely to metastasize. And 50% go to the brain.

The clinical trial results showed that after treatment, brain metastases shrank in 11 of 15 patients (73.3%), and brain metastases disappeared completely in 2 patients (13.3%). In addition to this extremely positive treatment outcome, the research team found that the drug was well tolerated, with no deterioration in participants' brain function or quality of life during the treatment period.

It is important to note that on June 5, 2022, the NEJM published a study with Trastuzumab deruxtecan in the treatment of HER2-low expression in patients with advanced breast cancer, which was directed by Dr. Shanu Modi of Memorial Sloan Kettering Cancer Center (MSKCC), showing that Trastuzumab deruxtecan extended progression-free survival by approximately 50% and overall survival by 40% in patients with advanced HER2-low expressing breast cancer compared with patients receiving standard chemotherapy.

This is the first instance where it has been proven that the drug can target the low-expressed HER2 protein and has a therapeutic effect on cancer. Approximately 50% of individuals with breast cancers that were once thought to be HER2-negative are actually HER2-low breast cancers, making them candidates for this ADC drug. This gives thousands of patients with advanced breast cancer new treatment options.

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