Brain metastases (BMs) are a frequent complication of non-small-cell lung cancer (NSCLC). Whole brain radiation therapy (WBRT) is a standard treatment for BMs, but favorable response of BMs with mutant epidermal growth factor receptor (EGFR) against tyrosine kinase inhibitors (TKIs) have also been reported. The aim of this study is to clarify the effect of TKIs alone without radiation therapy for BMs from EGFR-mutant NSCLC.
BMs from NSCLC with EGFR-mutation were enrolled. Gefitinib was administrated first, and erlotinib or afatinib was used at tumor progression. Erlotinib (or afatinib) was also selected for patients whose BMs had developed after gefitinib (or erlotinib). The primary endpoint was overall survival after BM (OS), and the secondary endpoints were maximum response to TKIs, time to progression of intracranial lesions, and time to salvage radiation therapy (RT).
In this study, 108 patients with BMs were enrolled. The types of mutations were as follows: exon 19 deletion in 62, exon 20 L858R in 39, and other types of mutations in 7 cases. During the follow-up period, 70 deaths were observed but only 17 of these deaths were owing to the progression of intracranial lesions. The medium OS was 20.9 months. The response rates of first-line and second-line TKIs were 76.9% and 70.6%, respectively. The medium time to progression of intracranial lesions was 14.5 months, and medium time to salvage RT was 19.0 months. Among the patients, gefitinib was administrated in 83 (first-line) and erlotinib in 59 (fist-line:22, second-line, 37) cases. The response rates of gefitnib and erlotinib were 76.8% and 78.6%, and the time to progression of intracranial lesions after gefitinib and erlotinib were 13.9 and 20.3 months, respectively. We could not find any significantly different response of BMs to TKIs owing to the types of mutations.
TKIs showed favorable control of BMs harboring EGFR-mutation without RT. At progression, other types of TKIs still showed excellent effect. TKIs first treatment could postpone RT, and feasible for BMs from EGFR-mutant NSCLC.
Clinical trial identification
Legal entity responsible for the study
Chiba Cancer Center
JSPS KAKENHI grant
All authors have declared no conflicts of interest.