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Novel HER2-targeted therapies for HER2-positive metastatic breast cancer
Siddharth Kunte1, Jame Abraham1, Alberto J Montero2
1Cleveland Clinic, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio.
Abstract:
Human epidermal growth factor receptor 2 (HER2) is overexpressed in approximately 20% of all breast cancers. Before the development of HER2-directed monoclonal antibodies, HER2-positive breast cancer was associated with a rather poor prognosis. With the advent of monoclonal HER2-targeting antibodies (trastuzumab and pertuzumab) and antibody-drug conjugates (trastuzumab emtansine [T-DM1] and trastuzumab deruxtecan), clinical outcomes for HER2-positive breast cancer have dramatically changed, and a greater proportion of patients in the nonmetastatic setting are cured. However, in the metastatic setting, resistance to anti-HER2 treatments still remains a major therapeutic challenge, underscoring the importance of developing novel HER2-directed therapies. Over the last year, there has been a dramatic shift in the current treatment paradigms for HER2-positive metastatic breast cancer, with recent U.S. Food and Drug Administration approvals of trastuzumab deruxtecan (DS-8201), neratinib, and tucatinib in combination with trastuzumab and capecitabine. The authors summarize recent phase 3 data with novel HER2-targeted therapies as well as phase 1 and 2 data with other novel HER2-targeting agents.
Insights
Novel HER2-targeted therapies, including antibody-drug conjugates and new FDA-approved agents, are improving outcomes for HER2-positive breast cancer. Resistance in metastatic disease necessitates ongoing development of innovative treatments.
Area of Science:
- Oncology
- Medical Research
- Pharmacology
Background:
- Human epidermal growth factor receptor 2 (HER2) overexpression occurs in about 20% of breast cancers.
- HER2-positive breast cancer historically had a poor prognosis before targeted therapies.
- Advancements in HER2-directed therapies have significantly improved patient outcomes, especially in the nonmetastatic setting.
Purpose of the Study:
- To review recent clinical trial data on novel HER2-targeted therapies for breast cancer.
- To highlight the evolving treatment landscape for HER2-positive metastatic breast cancer.
- To discuss emerging HER2-targeting agents and their potential impact.
Main Methods:
- Review of recent Phase 3 clinical trial data.
- Analysis of Phase 1 and 2 data for novel HER2-targeting agents.
- Summary of recent FDA approvals for HER2-positive metastatic breast cancer treatments.
Main Results:
- Monoclonal antibodies and antibody-drug conjugates have transformed HER2-positive breast cancer treatment.
- Recent approvals include trastuzumab deruxtecan, neratinib, and tucatinib combinations.
- Resistance to current anti-HER2 treatments in metastatic settings remains a significant challenge.
Conclusions:
- Novel HER2-targeted therapies have dramatically improved outcomes for HER2-positive breast cancer patients.
- Despite progress, therapeutic resistance in the metastatic setting requires continued research and development of new agents.
- The treatment paradigm for HER2-positive metastatic breast cancer is rapidly evolving with new therapeutic options.
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