Advancements in Treatment Selection and Sequencing in HER2-Positive Metastatic Breast Cancer: Insights from ASCO 2025 - Episode 9
Post-THP Strategies: HER2CLIMB-02 Data and Brain Metastases Management
Panelists discuss how HER2CLIMB-02 data showing benefit of tucatinib plus T-DM1 provides another treatment option, though its positioning in the evolving treatment landscape remains uncertain given other available regimens.
HER2CLIMB-02 and Treatment Sequencing
HER2CLIMB-02 evaluated T-DM1 plus tucatinib versus T-DM1 alone following CLEOPATRA regimen progression, demonstrating improved progression-free survival in the combination arm including patients with brain metastases. However, the combination increased toxicity compared to T-DM1 monotherapy, particularly elevated liver function tests since both agents can cause hepatotoxicity. The study's positioning in current treatment algorithms remains unclear given evolving first-line options.
The challenge with HER2CLIMB-02 relates to sequencing after tucatinib exposure, as rechallenging with tucatinib after prior exposure lacks established efficacy data. This consideration becomes more relevant as tucatinib-containing regimens move earlier in treatment sequences. T-DM1 alone maintains appeal for its tolerability profile, representing a viable option for patients prioritizing quality of life over maximum efficacy in later treatment lines.
CNS screening practices are evolving, with increasing adoption of baseline brain imaging at metastatic diagnosis to inform treatment selection. This approach has gained momentum with T-DXd CNS activity data, as brain metastases presence might influence first-line treatment choice between T-DXd and other options. Real-world experience includes cases where undetected CNS disease led to catastrophic progression despite good systemic control, reinforcing screening importance.
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