Penetration of the blood-brain barrier by avitinib and its control of intra/extra-cranial disease in non-small cell lung cancer harboring the T790M mutation

Lung Cancer : Journal of the International Association for the Study of Lung Cancer
Hanping WangMengzhao Wang

Abstract

Avitinib is an oral, potent, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor selective for the EGFR T790 M mutation. We report the safety, intra-/extracranial efficacy, and the blood-brain barrier (BBB) penetration rate of avitinib (NCT02330367). Non-small cell lung cancer (NSCLC) patients with the EGFR T790 M mutation were orally administered avitinib (150-300 mg) twice daily for cycles of 28 continuous days. Blood and cerebrospinal fluid samples (2 ml each) were collected on day 29 in available patients with brain metastases, and the tumor response was assessed. Sixteen NSCLC patients were included, of whom nine (60.0%) achieved a partial response, and five (33.3%) achieved stable disease. Median progression-free survival (PFS) and overall survival were 247 days (95% confidence interval (CI): 154.8-339.2) and 536 days (95%CI: 363.6-708.4), respectively. The median intracranial PFS of seven brain metastases patients was 142 days (95% CI 31.1-252.9). Blood and cerebrospinal fluid analysis of five brain metastases patients showed the BBB penetration rate to be 0.046%-0.146%. The most frequent adverse events were mild and reversible hepatic transaminases elevating (10/16, 62.5%) and diarrhea (4/16, ...Continue Reading

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Citations

Sep 13, 2019·Bioscience Trends·Xu YaoJianjun Gao
Oct 31, 2020·Current Opinion in Oncology·Lingyun YeFei Zhou
Aug 21, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ligang XingJinming Yu
Mar 30, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Rui-Fang DongLing-Yi Kong
Aug 28, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Yuan LiangJie Zhang

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