Management of brain metastases (BM) in patients with epithermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) is a challenge, since many patients suffer from BM despite the high efficacy of EGFR tyrosine kinase inhibitors (TKIs) to other lesions. We compared the treatment strategy of initial whole-brain radiotherapy (WBRT), stereotactic radiotherapy (SRT) or treatment with TKIs alone for patients with EGFR mutant NSCLC with BM at diagnosis.
We retrospectively analyzed medical records of patients diagnosed as advanced EGFR mutant NSCLC between Jan 2006 and Jan 2012. We defined central nervous system (CNS) failure as radiological progress and symptoms likely due to CNS progression (i.e. unusual headache, focal neurologic deficit, and change in mental status). CNS event free survival (EFS) and systemic progression free survival (PFS) were analyzed using Kaplan-Meier method and log-rank test.
A total of 180 patients were found to have EGFR mutation and 155 patients started EGFR-TKI as first line systemic chemotherapy. Of those, 38 patients had BM at diagnosis. The median age was 62.5 years (range 36-78). Thirty patients (79%) were female. ECOG performance status was 0-1 in 29 patients (76%). Twenty-two patients (58%) had EGFR exon 19 deletion and others had L858R point mutation. Initial therapy was WBRT, SRT and EGFR-TKIs in 16, 7, and 15 patients. When patients with BM were compared with 117 patients without BM, the median CNS EFS were 492 days and 1330 days, respectively (p < 0.001) and systemic PFS were 350 days and 504 days (p = 0.009). The median CNS EFS of WBRT, SRT and EGFR-TKI groups were 604 days, 700 days and 477 days, respectively. When WBRT and SRT groups were combined as radiotherapy (RT) group, CNS EFS was significantly prolonged in RT group compared to EGFR-TKI group (median 604 days vs. 477 days, p = 0.02). Systemic PFS of WBRT, SRT and TKI groups were 260 days, 398 days and 469 days, with no difference between these three groups.
Cranial RT prior to TKIs achieved better CNS disease control in patients with advanced EFGR mutant NSCLC with BM. No difference in systemic PFS was found with the initial treatment modality.
Clinical trial identification
Y. Goto: membership on an advisory board or board of directors Lilly, Boehringer Ingelheim, Taiho. Y. Ohe: membership on an advisory board or board of directors Chugai, AstraZeneca, Lilly, Boehringer Ingelheim, Novartis, ONO, BMS. All other authors have declared no conflicts of interest.