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Asia Pac J Clin Oncol. 2017 Oct;13(5):e531-e533. doi: 10.1111/ajco.12643. Epub 2016 Dec 22.

Afatinib successfully treated leptomeningeal metastasis during erlotinib treatment in a patient with EGFR-mutant (Exon18:G719S) lung adenocarcinoma as a second-line chemotherapy.

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Department of Thoracic Malignancy, Osaka Prefectural Hospital Organization Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Habikino City, Osaka, Japan.


Exon18 mutations are detected in 3.6% of epidermal growth factor receptor mutations. Exon 18 mutations as driver mutations have higher sensitivities in vitro to second-generation (G)-tyrosine kinase inhibitors (TKIs) than to first G- and third G-TKIs at clinically relevant doses. In clinical trial, first G-TKIs have moderate but insufficient efficacy, and afatinib was more active in uncommon epidermal growth factor receptor mutations. Here, we present a case of a woman who was initially prescribed erlotinib for lung adenocarcinoma with an exon18 mutation. She developed a leptomeningeal metastasis during treatment and was switched to afatinib. Subsequently, her symptoms improved and she is currently treated with maintenance afatinib therapy. This report suggests improved efficacy of afatinib compared to erlotinib for refractory leptomeningeal metastasis in exon18 mutation.


afatinib; exon18 mutation; leptomeningeal metastasis; uncommon mutation

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