Current challenges and unmet needs in treating patients with human epidermal growth factor receptor 2-positive
Matti Aapro1, Fatima Cardoso2, Giuseppe Curigliano3
1Breast Center, Clinique de Genolier, Route du Muids 3, PO Box 100, 1272, Genolier, Switzerland.
Abstract:
Human epidermal growth factor receptor 2 oncogene (HER2-positive) overexpression/amplification occurs in less than 20% of breast cancers and has traditionally been associated with poor prognosis. Development of therapies that target HER2 has significantly improved outcomes for patients with HER2-positive advanced breast cancer (ABC). Currently available HER2-targeted agents include the monoclonal antibodies trastuzumab, pertuzumab, and margetuximab, the small-molecule inhibitors lapatinib, tucatinib, neratinib, and pyrotinib, as well as the antibody-drug conjugates trastuzumab emtansine and trastuzumab deruxtecan. Optimal sequencing of these agents in the continuum of the disease is critical to maximize treatment outcomes. The large body of clinical evidence generated over the past 2 decades aids clinicians in treatment decision-making. However, patients with HER2-positive ABC and specific disease characteristics and/or comorbidities, such as leptomeningeal disease, brain metastases, or cardiac dysfunction, are generally excluded from large randomized clinical trials, and elderly or frail patients are often underrepresented. In addition, there is great inequality in the accessibility of approved drugs across countries. This article addresses various challenging clinical situations when treating patients with HER2-positive ABC. The objective is to provide guidance to clinicians on how and when HER2-targeted therapies and additional treatments can be best implemented in routine clinical practice, on the basis of existing clinical evidence and expert opinion where needed.
Insights
Treatment strategies for HER2-positive advanced breast cancer (ABC) are evolving. This review guides clinicians on optimizing HER2-targeted therapies for challenging patient cases and diverse clinical scenarios.
Area of Science:
- Oncology
- Pharmacology
Background:
- HER2-positive breast cancer, though less common, historically had a poor prognosis.
- Targeted therapies have dramatically improved outcomes for HER2-positive advanced breast cancer (ABC).
- A range of HER2-targeted agents are available, including monoclonal antibodies, small-molecule inhibitors, and antibody-drug conjugates.
Purpose of the Study:
- To provide guidance on optimizing HER2-targeted therapies in challenging clinical situations for patients with HER2-positive advanced breast cancer.
- To address treatment decision-making for patients with specific comorbidities or disease characteristics often excluded from trials.
- To offer expert opinion where clinical evidence is limited, focusing on routine clinical practice.
Main Methods:
- Review of existing clinical evidence on HER2-targeted therapies for advanced breast cancer.
- Incorporation of expert opinion to address complex patient scenarios and treatment sequencing.
- Focus on practical implementation in routine clinical practice.
Main Results:
- Optimal sequencing of HER2-targeted agents is crucial for maximizing treatment outcomes.
- Challenges include managing patients with leptomeningeal disease, brain metastases, cardiac dysfunction, and underrepresented populations (elderly, frail).
- Inequalities in drug accessibility across countries present an additional challenge.
Conclusions:
- This article provides practical guidance for clinicians managing HER2-positive advanced breast cancer.
- It emphasizes evidence-based and expert-opinion-driven approaches for complex cases.
- The goal is to enhance treatment outcomes through judicious use of HER2-targeted therapies.
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