Epidemiology, clinical outcomes, and unmet needs of patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases: A systematic literature review

There is an increasing need for developing effective therapies for managing intracranial disease in patients with human epidermal growth factor receptor 2-positive (HER2 +) metastatic breast cancer and brain metastases (BM), as this population is growing and has historically been excluded from large clinical trials. In this systematic literature review, we aimed to provide a comprehensive overview of the epidemiology, unmet needs, and global treatment landscape for patients with HER2 + metastatic breast cancer and BM, with a particular focus on heterogeneity across clinical trial designs in this setting.We conducted literature searches of PubMed and select congress websites up to March 2022 and filtered for publications with a significant focus on epidemiology, unmet needs, or treatment outcomes in patients with HER2 + metastatic breast cancer and BM.Key clinical trials of HER2-targeting treatments for HER2 + metastatic breast cancer had varying eligibility criteria relating to BM, with only two trials-HER2CLIMB and DEBBRAH-including patients with both active and stable BM. We also observed variance across assessed central nervous system (CNS)-focused endpoints (CNS objective response rate vs CNS progression-free survival vs time to CNS progression) and robustness of statistical analysis (prespecified vs exploratory).There is an unmet need for standardization of clinical trial design for patients with HER2 + metastatic breast cancer and BM, to aid the interpretation of the global treatment landscape and ensure patients with all types of BM can access effective treatments.