New Systemic Therapy Strategies for HER2-Positive Metastatic Breast Carcinoma

Abstract

HER2 positivity is predictive of the response to anti-HER2 therapies. The treatment of HER2-positive tumors is continuously improving through the development of new anti-HER2-directed agents. Many different anti-HER2 therapies are now available which belong to the classes of anti-HER2 antibodies, tyrosine kinase inhibitors (TKI) and antibody-drug conjugates (ADC). A combination of trastuzumab, pertuzumab and a taxane (THP) remains the preferred first-line (1L) therapy, whereas T‑DXd is the new standard for 2L metastatic breast cancer based on a highly significant improvement in progression-free survival compared to T-DM1 as shown in the DESTINY-Breast03 study. A tucatinib-based regimen (dual anti-HER2 therapy with trastuzumab and tucatinib plus capecitabine) is the preferred 3L option, which may already be used for 2L treatment in patients with active brain metastases. Different anti-HER2 therapies are available in the 3L setting and beyond. Molecular biomarkers in addition to the quantification of HER2 expression, such as the PD‑L1 status and PIK3CA mutations, can further guide the decision-making process in the future.