Updates on targeting human epidermal growth factor receptor 2-positive breast cancer: what's to know in 2021

To highlight recent practice changing clinical trials, focusing on those leading to new drug approvals, in human epidermal growth factor receptor 2-positive (HER2+) breast cancer.

The improved disease-free survival of adjuvant trastuzumab emtansine (T-DM1) over trastuzumab in patients with residual disease has made neoadjuvant sequencing of therapy standard for most patients with early stage disease. In patients with metastatic HER2+ breast cancer, trastuzumab deruxtecan has recently shown dramatically improved efficacy over T-DM1. Tucatinib is an oral tyrosine kinase inhibitor with best in class blood-brain barrier penetration. Margetuximab, a novel HER2-targeted chimeric monoclonal antibody with an engineered Fc receptor designed to activate local immune response, was recently approved in heavily pretreated patients based on modest but significant improvement in progression-free survival.

Patients with HER2+ breast cancer have a variety of therapeutic options in the early stage and metastatic setting. Optimal sequencing of therapy will depend on patient-specific factors such as site of tumor progression and underlying comorbidities. De-escalation of the first-line metastatic regimen may be considered in select patients with hormone positive/HER2+ breast cancer, by using endocrine therapy instead of chemotherapy in combination with HER2-targeted therapy, which may improve side effects without sacrificing efficacy.