Population-Based Analysis of Outcomes for Patients With Brain Metastases From Epidermal Growth Factor Receptor Mutation Positive Non-Small Cell Lung Cancer Treated With Tyrosine Kinase Inhibitor Alone or Combined With Radiotherapy

Abstract

With modern therapies, the median survival of patients with brain metastases (BrM) from non-small cell lung cancer (NSCLC) with epidermal growth factor receptor mutation (EGFRm) may exceed 1-2 years. BrM directed therapies must therefore carefully balance treatment efficacy and late toxicity. Although some tyrosine kinase inhibitors (TKI) exhibit intracranial activity, there is no level-one evidence to support up-front treatment of BrM using TKI without radiotherapy (RT). This study aimed to compare the outcomes of patients with BrM from EGFRm NSCLC treated with initial RT and TKI, versus TKI alone.All patients who received a TKI (gefitinib, erlotinib, afatinib, or osimertinib) in British Columbia for NSCLC between January 2010 to 2018 were identified in a provincial pharmacy database. Patients were then screened for pathologic diagnosis of EGFRm, and radiologic diagnosis of BrM. These patients were categorized as receiving either TKI alone or RT with TKI for treatment of their BrM. Patients who received RT were cross-referenced with a provincial RT database to determine radiotherapy prescriptions and were classified as having received whole brain (WBRT) with TKI or stereotactic RT/radiosurgery (SRS) with TKI. Patients were excluded if they discontinued TKI after RT or ever received surgery for BrM. Overall survival (OS) and intracranial progression free survival (iPFS) were calculated from the date of BrM diagnosis using Kaplan-Meier analysis. Log rank test was used for comparison between groups, and Cox proportional hazards model was used for multivariate analysis.A total of 167 patients were included for analysis with a median follow up of 45 months. Median OS was 19 months with WBRT (n = 76), 21 months with SRS (n = 45), and 6 months with TKI alone (n = 46), P < 0.01. In patients who had WBRT, iPFS was better than in those having TKI alone [HR 4.68 (2.07-10.56); P < 0.01] or SRS [HR 2.43 (1.20-4.91); P < 0.01]. On multivariate analysis: advanced age, worse performance status, presence of extracranial metastasis, greater than 10 B.M. and type of treatment (TKI alone versus RT with TKI) were associated with inferior OS.This study showed that compared to treatment with TKI alone, the addition of RT for BrM is associated with an improved OS in patients with EGFRm NSCLC. These results are complementary to the growing body of retrospective data suggesting an inferior survival associated with TKI alone compared to RT with TKI for treatment of BrM in patients with EGFRm NSCLC. Prospective studies are required to further guide the best approach to managing this patient population.T. Kong: None. A. Nichol: None. C. Ho: None. A. Benny: None. N. Chooback: None. I.M. Fraser: None. L. Gondara: None. S. Lefresne: None.