412O - Tyrosine kinase inhibitors without radiation therapy for brain metastases from EGFR-mutant adenocarcinoma of lung

Date 01 October 2012
Event ESMO Congress 2012
Session CNS tumors
Topics Central Nervous System Malignancies
Thoracic Malignancies
Presenter Toshihiko Iuchi
Authors T. Iuchi1, M. Shingyoji2, T. Sakaida1, S. Yokoi3, M. Itakura2, K. Kawasaki1, Y. Hasegawa1, H. Kageyama3, T. Iizasa2
  • 1Neurological Surgery, Chiba Cancer Center, 2608717 - Chiba/JP
  • 2Thoracic Disease, Chiba Cancer Center, 2608717 - Chiba/JP
  • 3Cancer Diagnosis, Chiba Cancer Center Research Institute, 2608717 - Chiba/JP



Whole-brain radiation therapy (WBRT) and/or stereotactic radiosurgery (SRS) are standard treatments for brain metastases (BMs). However, patients (pts) treated by radiation therapy (RT) have a risk of decline in learning and memory functions. The aim of this study is to clarify the efficacy and safety of chemotherapy without RT for BMs.

Materials and methods

BMs from lung adenocarcinomas (Ads) with EGFR-mutation were enrolled. As tyrosine kinase inhibitors (TKIs), gefitinib was used at first, and erlotinib was administrated at tumor progression. Erlotinib was also selected for pts in whom intracranial lesions appeared after gefitinib. The response to TKIs was evaluated on MRI. WBRT or SRS was performed only at tumor progression after TKIs. The primary endpoint was overall survival, and the secondary endpoints were maximum response to TKIs, progression-free survival and time to RT after diagnosis of BMs.


In this study, 37 pts were enrolled. The types of EGFR-mutations were as follows: Ex19 deletion (Ex19del) in 20, Ex21L858R in 14, and other types of mutations in 3 cases. The maximum response was PD in one, SD in 3, PR in 22 and CR in 9 pts (response rate: 83.8%). The progression-free and overall survival times were 8.9 and 28.3 months. The median time to RT (WBRT in 14 and SRS in 3 cases) from diagnosis of BMs was 14.3 months. During the follow-up period, 9 deaths were observed but none of them were owing to the intracranial lesions. Among these 9 pts, no RT was required in 2. Pneumonitis was observed in one case after gefitinib, but no other severe adverse event was observed. When we divided the pts owing to the types of mutations (Ex19del vs. others), response to TKI was superior in Ex19 deleted cases (p = 0.031), and the progression-free survival time was significantly longer in cases with Ex19del (14.5 months) in compared with those with other types of mutations (8.0 months, p = 0.002). In Ex19 deleted cases, TKIs could delay RT for 18.3 months.


TKIs showed favorable effect on control of EGFR-mutant BMs, and it delayed RT for more than one year. Ex19del was the significant predictor of response to TKIs in BMs. TKIs without RT was safe and acceptable treatment for BMs from EGFR-mutant lung Ads.


All authors have declared no conflicts of interest.