Looking Ahead in HER2+ mBC: Unmet Needs, Future Perspectives and Highlights From ASCO 2025
Panelists highlighted the impressive central nervous system activity of trastuzumab deruxtecan demonstrated in the DX12 trial, underscoring the need for multidisciplinary collaboration to optimize treatment of brain metastases and reduce reliance on whole-brain radiation, while acknowledging ongoing challenges in sequencing and patient selection amid evolving therapies.
The discussion concluded with a spotlight on recent advancements in the treatment of central nervous system (CNS) metastases in HER2-positive metastatic breast cancer, particularly the implications of new data from the DESTINY-Breast12 trial. This study highlighted the significant CNS activity of trastuzumab deruxtecan, showing a 70% intracranial response rate and approximately 60% progression-free survival at 12 months in patients with brain metastases. These results, alongside prior data from earlier trials, challenged the long-standing belief that large molecule drugs struggle to cross the blood-brain barrier, suggesting that the active payload of T-DXd is likely responsible for its robust intracranial efficacy.
This shift in understanding also raised the importance of evolving treatment strategies. The panel emphasized the critical need for multidisciplinary collaboration among oncologists, radiation oncologists, and neurosurgeons. In many community settings, patients with brain metastases are still routinely directed to receive whole-brain radiation, even when systemic therapies may offer effective, less toxic alternatives. A coordinated approach, with timely input from medical oncology, could help spare patients from unnecessary cognitive adverse effects and improve long-term outcomes.
In closing, the panel reflected on the broader treatment landscape and remaining challenges. While newer therapies offer unprecedented survival advantages, questions remain around optimal sequencing and the impact of early-line use on later treatment options. The overarching sentiment was one of cautious optimism: the tools and therapies now exist, but success will depend on refining patient selection and integrating evolving data into real-world practice. Ongoing research, education, and multidisciplinary collaboration will be key to maximizing the benefits of these promising treatments.
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