This protocol addresses patients with HER2-positive breast cancer who have developed leptomeningeal metastasis — spread of the malignancy to the leptomeninges. This represents a distinct and serious clinical situation that requires a dedicated, targeted management approach.
Two phase I/II studies have demonstrated good tolerance of intrathecal trastuzumab in HER2-positive breast cancer. A meta-analysis of 58 patients with HER2-positive breast cancer and leptomeningeal metastasis treated with intrathecal trastuzumab — alone or in combination with systemic pharmacotherapy — reported a median overall survival of 13.2 months.
Current evidence supports an intrathecal targeted therapy strategy for this population. This approach can be delivered alone or in combination with systemic pharmacotherapy, with dosing schedules differing between the two established trial regimens.
DOI: 10.1016/j.esmoop.2023.101624
Two phase I/II studies have shown a good tolerance of intrathecal trastuzumab in human epidermal growth factor receptor 2 (HER2)-positive breast cancer.
A meta-analysis of 58 patients with HER2-positive breast cancer and LM treated with intrathecal trastuzumab alone (n = 20) or in combination with systemic pharmacotherapy (n = 37) reported a median OS of 13.2 months.
In the first trial (NCT01373710), intrathecal trastuzumab was administered alone or in combination with systemic pharmacotherapy once weekly.
The recommended phase 2 dose (RP2D) was 150 mg.
In the other trial (NCT01325207), intrathecal trastuzumab was administered twice per week for 4 weeks, then weekly for 4 weeks and then every 2 weeks; the RP2D was 80 mg.
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