EGFR mutation status and survival after diagnosis of brain metastasis in non-small cell lung cancer.

Abstract

7542 Background: Non-small cell lung cancer (NSCLC) is the most frequent site of origin for brain metastases (BM), which affect 30%-40% of pts with advanced disease. A small subset of pts with NSCLC harbor mutations in the epidermal growth factor receptor (EGFR) that predict unique sensitivity to EGFR tyroskine kinase inhibitors (TKIs). The characteristics and behavior of BM in this population have not been well described. Methods: From August ‘04 to November ‘08, 373 NSCLC pts underwent EGFR mutation screening at our center; 93 of these developed BM at some time during their course. Clinical and treatment variables were collected by chart review. Survival was estimated using the Kaplan-Meier method and log-rank test. Multivariate predictors were assessed via Cox proportional hazards models. Results: Among the 93 pts with BM, 41 (44%) had an EGFR mutation, including 13 exon 19 del and 12 L858R. Brain was the first site of metastasis in 55/93 pts (59%) and the proportion did not differ by mutation status. 83% of pts with BM were treated initially with whole brain radiation, either alone (53%) or in combination with surgery (22%) or stereotactic radiosurgery (8%). 6 pts were treated with TKIs alone; all but 1 were EGFR mutant. Median survival from the time of BM was 10.5 mo. On univariate analysis, EGFR-mutated pts had prolonged survival after BM (12.0 mo vs. 7.3 mo, p = 0.05). Additional predictors of survival included age, performance status, number of BM and status of extracranial disease. On multivariate analysis, EGFR mutation status (HR 0.36, 95% CI 0.20- 0.63), age (HR 1.03, 95% CI 1.01-1.06) and active extracranial disease (HR 3.72, 95% CI 1.84-1.75) remained strong independent predictors of survival. The rate of development of leptomeningeal disease (7%) did not vary by EGFR mutation status, nor did the rate of intracranial recurrence. Cause of death was isolated intracranial progression in 9%; combined intra- and extracranial in 31%; and isolated extracranial in 38%. Conclusions: EGFR mutation status is a strong prognostic factor in NSCLC pts developing BM, independent of known prognostic factors including age, functional status, extracranial disease status and number of BM. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Gatekeeper Biogen Idec, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, MedImmune, Millennium, Roche, Schering-Plough, Telik Novartis