Highlighting the Evolving Landscape of HER2-Low Breast Cancer
The management of metastatic breast cancer (mBC) has undergone a paradigm shift with the identification of the HER2-low subgroup—defined as an immunohistochemistry (IHC) score of 1+ or 2+ with negative in situ hybridization (ISH). Historically, these patients were treated as HER2-negative, missing the targeted potential of anti-HER2 therapies. Trastuzumab deruxtecan (T-DXd), a next-generation antibody-drug conjugate (ADC), changed this landscape by demonstrating significant survival benefits in the DESTINY-Breast04 trial. However, the next frontier in clinical research focuses on whether T-DXd can be safely and effectively combined with other therapeutic agents to overcome resistance and enhance clinical outcomes.
The DESTINY-Breast08 phase 1b study was designed to address this question by evaluating T-DXd in combination with a variety of agents, including chemotherapy, immunotherapy, AKT inhibitors, and endocrine therapies, specifically for patients with HER2-low mBC. The results offer a critical early look at the safety signals and preliminary efficacy of these novel regimens.
