Advancements in Treatment Selection and Sequencing in HER2-Positive Metastatic Breast Cancer: Insights From ASCO 2025 - Episode 8
Evidence-Based Treatment Selection in Later-Line HER2+ Metastatic Breast Cancer: DESTINY-Breast12 Data and Tucatinib's Evolving Role
Panelists discuss how trastuzumab deruxtecan has demonstrated significant central nervous system activity in DESTINY-Breast12, making it an effective option before HER2CLIMB-based regimens, even in patients without existing brain metastases.
CNS Metastases Management
Central nervous system (CNS) metastases represent a critical unmet need in HER2-positive metastatic breast cancer management, with T-DXd showing significant CNS activity across multiple studies. DESTINY-Breast12 phase 3b/4 data demonstrated 60% 12-month progression-free survival and 71% overall response rate, with matching 71% intracranial response rate. This established T-DXd as an effective CNS-directed therapy, influencing treatment sequencing decisions regardless of baseline brain metastases status.
The HER2CLIMB regimen remains important for CNS management, representing the first trial to allow active brain metastases enrollment. This study demonstrated both progression-free and overall survival benefits while showing delayed time to brain metastases development. The regimen's efficacy extends beyond CNS disease to visceral disease control, making it valuable across patient populations despite higher pill burden compared to alternatives.
Current practice varies regarding baseline CNS screening, with some oncologists implementing routine brain imaging at metastatic diagnosis while others use symptom-directed approaches. Progressive CNS imaging at each line of therapy progression is becoming more standard, given increasing brain metastases rates with successive treatment lines. Stereotactic radiosurgery integration provides additional management options, particularly when small numbers of lesions are detected early through screening protocols.
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