Subsequent Brain Metastasis Responses to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in a Patient with Non-small-cell Lung Cancer

In response to the paper by Popat et al. "Recurrent responses to non-small-cell lung cancer brain metastases with erlotinib", we wish to report a similar case and to provide comments. A 32-year-old Chinese never-smoker female presented a primary lung adenocarcinoma with brain metastasis and three subsequent responses to EGFR tyrosine kinase inhibitors (gefitinib and erlotinib). Direct sequencing of epidermal growth factor receptor (EGFR) gene exons 18 to 21 and K-ras gene was performed on tissue obtained from initial biopsies and post-chemotherapy surgical specimens. An EGFR exon 21 L858R point mutation was identified on pre- and post-chemotherapy samples. K-ras mutations and EGFR exon 20 T790M point mutations were not detected. Moreover, EGFR protein overexpression was observed by immunohistochemistry as well as EGFR gene high polysomy by fluorescent in situ hybridization. These case suggest that re-challenging patients with NSCLC several times with EGFR-TKI should be considered when progressive disease is observed under chemotherapy. However, we do not yet know whether this option should be considered in light of tumor molecular evaluation, or whether it should be proposed to patients who experienced a clinical response after a first administration.