139PD - Lifetime incidence of brain metastases (BM) in EGFR-mutant (M+) lung cancer treated with first-line EGFR TKIs

Date 14 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Targeting EGFR and ALK driven tumours
Topics Anticancer agents
Non-Small Cell Lung Cancer
Biological Therapy
Presenter David Ng
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors D.Z. Ng1, W.L. Tan2, W.S. Ong3, E.M. Gan1, A. Jain2, E. Tan2, D. Tan2
  • 1Yong Loo Lin Undergraduate School Of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228 - Singapore/SG
  • 2Department Of Medical Oncology, National Cancer Center, 169610 - Singapore/SG
  • 3Biostatistics Unit, National Cancer Center, 169610 - Singapore/SG



BM commonly occur in EGFR M+ NSCLC and remain an unmet medical need. This study aims to determine (1) lifetime incidence of brain metastases (BM) in EGFR M+ lung adenocarcinoma (LUAD), (2) likelihood of BM development while on EGFR TKI treatment, and (3) risk factors associated with BM development in patients treated with first-line EGFR TKIs.


211 patients diagnosed in between August 2009 and February 2013 with advanced EGFR M+ LUAD (mainly exon 19 or 21 mutations), and who received 1st line EGFR TKI, were included in this study. Patient demographics, presence/ absence of BM at initial diagnosis, pattern of relapse, type of mutation, and choice of EGFR TKI were recorded. BM-free survival (BMFS) was estimated using the Kaplan–Meier method. Univariate and multivariate (MVA) Cox regression analyses were used to identify factors associated with risk for BM development.


63/211 (29.9%) of patients had baseline BM while 137 did not, and 11 had missing data. Of the 137 pts, 84 (61.3%) were female, 116 (84.7%) Chinese, 108 (78.8%) never-smokers and the median age was 65 yrs (range: 40–84). 123 (89.8%) patients received 1st line gefitinib, while the rest had erlotinib (4.4%) or afatinib (5.8%). After a median follow-up of 31.3m, 40/137 (29.2%) patients developed BM. 15/40 (37.5%) had BM during 1st line TKI. Of the remaining 25 patients with BM after first-line TKI, 14 received further TKI beyond first-line. Cumulative incidence rate of BM (CIBM) at 24-m was 29.2% (95% CI 21.3–39.3). On MVA, presence of liver metastases at diagnosis (HR 2.76, 95% CI 1.25–6.10) was the strongest predictor for BMFS. Among the 97 patients who first progressed in non-CNS sites, there was no significant difference in time to BM development after first disease progression between patients who received TKI beyond progression (23/76) and those who did not (1/21) (p = 0.123).


The lifetime incidence of BM for EGFR M+ LUAD is 48.8% in patients predominantly treated with gefitinib. In those without baseline BM, CIBM at 12-m and 24-m was 13.7% and 29.2% respectively. Presence of liver metastases at diagnosis may predict higher risk of development of BM in EGFR M+ LUAD.

Clinical trial identification

Legal entity responsible for the study

National Cancer Centre Singapore


National Cancer Centre Singapore


All authors have declared no conflicts of interest.