This protocol covers the management of central nervous system metastases in patients with HER2-positive breast cancer who present with asymptomatic or only minimally symptomatic brain involvement and a preserved general performance status.
The patient has HER2-positive breast cancer with brain metastases that are asymptomatic or oligosymptomatic. General status is preserved. In this setting, upfront whole-brain radiotherapy (WBRT) is not the mandatory immediate step, and systemic approaches are actively considered to defer it.
Systemic targeted therapy forms the backbone of management in this scenario, with the primary clinical goal of delaying whole-brain radiotherapy. Several HER2-directed combination regimens have been evaluated for intracranial activity in this population — the complete set of options, how to select among them, and the full sequencing algorithm are contained in the structured protocol.
Systemic treatment of asymptomatic or oligosymptomatic BMs should be considered to delay WBRT in HER2-positive breast cancer patients with a preserved general status.
In patients without neurosurgical indication and with preserved neurological status (PS 0-2), previously treated with trastuzumab but capecitabine–lapatinib-naïve, the combination of lapatinib and capecitabine produced a brain response rate of 38% in patients with pre-irradiated BM and of 66% in patients with treatment-naïve BM.
The combination of tucatinib, capecitabine and trastuzumab was tested in a third-line phase III trial with half of the patients presenting with BM (HER2CLIMB).
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