Sequencing Therapies in the Third-Line and Beyond for Patients With HER2+ Metastatic Breast Cancer
Doctors Laura Spring and Manali Bhave discuss summarize their recommended sequence of systemic therapy options for HER2-positive metastatic breast cancer, from first-line taxane and dual HER2 blockade through later lines with T-DM1, tucatinib, and other regimens.
EP: 1.Clinical Scenario: A 57-Year-Old Woman With Metastatic Breast Cancer
EP: 2.Current First-Line Systemic Therapy Options for HER2+ Metastatic Breast Cancer
EP: 3.Key Clinical Trials in the First-Line Treatment of HER2+ Metastatic Breast Cancer
EP: 4.Standard of Care Regimens for Second-Line Treatment of HER2+ Metastatic Breast Cancer
EP: 5.Sequencing Therapies in the Third-Line and Beyond for Patients With HER2+ Metastatic Breast Cancer
EP: 6.Clinical Scenario: A 65-Year-Old Post-Menopausal Woman With Metastatic Breast Cancer
EP: 7.Approaches to Mutation Testing for Patients With HR+/HER2-low mBC and ET-Resistant Disease
EP: 8.Factors for Consideration When Choosing Among Options for Patients with ET-resistant ER+/HER2- mBC
EP: 9.Sequencing Antibody-Drug Conjugates (ADCs) in HR+/HER2-Low Metastatic Breast Cancer
EP: 10.Exciting Data in the Treatment of HER2-low from SABCS 2023
The discussion moves to considering other treatment options after progression on trastuzumab deruxtecan (T-DXd). Bhave asks Spring if she would ever use the tucatinib/trastuzumab/capecitabine (HER2CLIMB) regimen in the second-line setting.
Spring responds that the HER2CLIMB regimen is usually reserved for patients with progressive brain metastases, as it has impressive CNS activity. However, emerging data also shows T-DXd has remarkable CNS penetration. For patients without brain metastases, Spring typically uses T-DXd second-line and saves HER2CLIMB for later lines.
Bhave agrees and outlines her typical sequence as T-DXd second-line, then HER2CLIMB third-line, followed by other later options like tyrosine kinase inhibitors (TKIs) with capecitabine, or considering T-DM1 despite lack of data after T-DXd. She asks Spring about her approach in the third-line and beyond setting.
Spring notes the lack of data to definitively guide sequencing after T-DXd and HER2CLIMB. Factors like pace of disease, sites of metastases, and previous durations of response can help weigh using chemotherapy plus anti-HER2 therapy versus trying T-DM1. For brain metastases, she would consider capecitabine which has CNS activity.
Both agree there are many options like TKIs, chemotherapy/anti-HER2 combinations, and margetuximab but limited data on optimal sequencing, highlighting an unmet need for more evidence in later treatment lines. Ultimately, a personalized approach is required based on each patient's disease characteristics and prior therapies.
This summary was AI-generated and edited for clarity.
