A Single-Institution Review of Patients with EGFR-positive Non-Small Cell Lung Cancer with Brain Metastases at Presentation

Abstract

Approximately 10% of patients with non-small cell lung cancer (NSCLC) present with brain metastases (BM) at time of initial diagnosis. The prognosis of these patients is poor, with a median survival of 8-10 months. However, a subset of patients with NSCLC, adenocarcinoma type, harboring mutations in the epidermal growth factor receptor (EGFR) gene have been shown to have a significant response to EGFR tyrosine kinase inhibitors, which in turn improves survival outcomes. Recent literature has suggested that BM from EGFR-positive NSCLC may have higher response rates and more favorable control of intracranial disease. This retrospective review sought to characterize the course and outcomes of patients with EGFR-positive NSCLC with brain metastases at initial presentation. This was an IRB-approved single-institution database of patients with NSCLC who had undergone EGFR testing between January 2010 and December 2018. Patients with EGFR-positive NSCLC were identified. Data regarding patient characteristics, pathologic features, and treatment approach, including BM management and systemic therapy, were collected. Dates of recurrences, last follow-up, and date of death were recorded. Time to recurrence and overall survival were evaluated with Kaplan-Meier and compared using log-rank testing. One hundred and twenty-three patients with NSCLC and brain metastases at initial presentation underwent EGFR-testing. Of those, we identified 36 patients with pathologic confirmation of EGFR-positive adenocarcinoma. The mean age of patients at diagnosis was 65.8 years (range 52-87). Two patients had leptomeningeal disease at diagnosis. Five patients presented with solitary BMs. The mean number of brain metastases was 11.7 (range 1-38). The majority of patients (n=23, 62%) underwent radiosurgery as initial management of BM, while seven (19%) patients received whole brain radiation therapy. Four (11%) patients received EGFR-targeted therapy alone; all underwent SRS upon progression. Of the 34 patients who underwent treatment of their BM, 20 (59%) developed recurrence, and eight patients (23.5%) developed leptomeningeal disease. Median survival for the cohort was 1.4 years. Median time to BM recurrence was not significantly different between patients undergoing EBRT versus SRS (median 33.7 vs 35.7 weeks, respectively, p=0.58). This is one of the largest series to date analyzing EGFR-positive NSCLC with BM at presentation. Despite several treatment approaches, outcomes remain poor for this patient population, with overall survival of 1.4 years and almost one-quarter of patients developing leptomeningeal disease. This population warrants further study in order to better optimize therapy.