Newly Approved and Emerging Agents in HER2-Positive Metastatic Breast Cancer

Human epidermal growth factor receptor 2-positive breast cancer (HER2+ BC) is an aggressive tumor type, accounting for 15% to 20% of the approximately 300,000 new BC cases in the United States each year. The goal of this review is to discuss the evolving landscape of therapies for HER2+ metastatic BC (mBC). Targeted therapies that have been the standard of care (SOC) for HER2+ mBC for almost a decade have greatly improved patient outcomes. The SOC for the first-line treatment of HER2+ mBC continues to be HER2-targeted monoclonal antibodies (mAbs) + a taxane, but recent updates in the second-line setting favor use of a newer HER2-targeted antibody-drug conjugate (ADC), trastuzumab deruxtecan, versus the prior SOC ADC, trastuzumab emtansine. Numerous options are now available in the third line and beyond, including tyrosine kinase inhibitor (TKI) regimens, newer mAbs, and other ADCs. The optimal course of treatment for individual patients can be guided by location of metastases, prior therapies, concomitant biomarkers, and monitoring and management of adverse events. Ongoing trials will further the evolution of the HER2+ mBC treatment landscape. Furthermore, next-generation ADCs, TKIs, and classes of drugs that have not been approved for the treatment of HER2+ mBC, including immune checkpoint inhibitors and cyclin-dependent kinase 4 and 6 inhibitors, are also being evaluated for their efficacy in the first and second line. Although the influx of new drugs may complicate treatment decisions for physicians, having a multitude of options will undoubtedly further improve patient outcomes and patient-centered care.