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Top Line: What is the intracranial activity of the pan-HER inhibitor, pyrotinib, among patients with HER2+ breast cancer brain metastases?

The Study: PERMEATE was a phase 2 Chinese trial with 2 cohorts of patients with brain metastases from HER2+ breast cancer that were either a) radiation-naive (n=59, 76%) or b) progressive after prior radiation (n=19, 24%). In the latter group, most patients (58%) had prior SRS alone while the rest had prior whole brain RT (26%) or a combination of WBRT and SRS (16%). The median time since prior RT was 10.4 months. All patients received pyrotinib and capecitabine. Among those with radiation-naive brain mets, the objective response rate was 74.6%, which included 12% complete and 63% partial responses. In this cohort, the CNS response rate exceeded the non-CNS response rate (70.4%). The CNS control rate (response + stable disease) was 93.2%. Median duration of response was 12.5 months. The CNS response rate exceeded non-CNS response rate Response was less robust in the previously irradiated cohort with an objective response rate of 42.1% (5% CR, 47% PR), and a CNS control rate of 63.2%. In this cohort, CNS response rate was lower than the non-CNS response rate (50%). Median duration of response was 7.7 months. So, here we have evidence that pyrotinib and capecitabine are effective for brain metastases and that their intracranial activity is comparable to extracranial activity. The challenge is that there are several other HER2 therapy combinations that are also effective for HER2 brain metastases depending on the scenario. These include high dose trastuzumab and pertuzumab, trastuzumab emtansine, tucatinib, and trastuzumab deruxtecan (see helpful review here). 

TBL: The CNS response rate for pyrotinib plus capecitabine is 74.6% for patients with radiation-naive brain metastases and 42.1% for progressing brain metastases after radiation. | Yan, Lancet Oncol 2022

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