Newly Approved and Emerging Agents in HER2-Positive Metastatic Breast Cancer
Stephanie L Graff1, Fengting Yan2, Yara Abdou3
1Ambulatory Patient Center, Lifespan Cancer Institute, Legorreta Cancer Center at Brown University, Rhode Island Hospital, Providence, RI.
Abstract:
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.
Insights
The treatment landscape for HER2-positive metastatic breast cancer (mBC) is rapidly evolving with new targeted therapies and antibody-drug conjugates (ADCs). These advancements offer improved outcomes and more personalized treatment options for patients with HER2+ mBC.
Area of Science:
- Oncology
- Medical Therapeutics
- Clinical Research
Background:
- Human epidermal growth factor receptor 2-positive breast cancer (HER2+ BC) represents 15-20% of US breast cancer cases.
- HER2+ metastatic breast cancer (mBC) is an aggressive subtype requiring specialized treatment strategies.
- Targeted therapies have significantly improved outcomes for HER2+ mBC patients over the past decade.
Purpose of the Study:
- To review the current and emerging therapeutic options for HER2+ metastatic breast cancer.
- To discuss the evolving treatment paradigms in first-line, second-line, and later settings.
- To highlight factors influencing treatment decisions and future directions in HER2+ mBC therapy.
Main Methods:
- Literature review of clinical trials and therapeutic advancements in HER2+ mBC.
- Analysis of standard of care (SOC) treatments and newer agents, including antibody-drug conjugates (ADCs) and tyrosine kinase inhibitors (TKIs).
- Discussion of ongoing research and novel drug classes being evaluated for HER2+ mBC.
Main Results:
- First-line SOC for HER2+ mBC remains HER2-targeted monoclonal antibodies plus a taxane.
- Trastuzumab deruxtecan is favored over trastuzumab emtansine in the second-line setting.
- Multiple treatment options, including TKIs, mAbs, and ADCs, are available for third-line and beyond treatment.
Conclusions:
- The treatment of HER2+ mBC is characterized by an expanding array of therapeutic choices.
- Treatment decisions should consider metastasis location, prior therapies, biomarkers, and adverse event management.
- Ongoing clinical trials and novel drug classes promise further improvements in patient outcomes and personalized care for HER2+ mBC.
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