Brain Metastases from Non-Small Cell Lung Cancer: Current Evidence in Management Using Tyrosine Kinase Inhibitor and Whole-Brain Radiation Therapy

Introduction

The annual incidence of lung cancer in 2012 in the United States was 226 160 patients (14% of all cancer patients), and an estimated 160 340 patients (28% of cancer mortality) will die of the disease ( ). About 20–44% of patients with lung cancer will develop brain metastases ( ; ). Patients with non-small cell lung cancer (NSCLC) presenting with single or oligometastatic disease can be treated with neurosurgery or stereotactic radiosurgery (SRS). Most patients present with multiple brain metastases and are candidates for whole-brain radiation therapy (WBRT). Prognosis remains poor in patients with brain metastases and this population is generally underrepresented in clinical trials.

The epidermal growth factor receptor (EGFR) mutation is a member of the ErbB family of receptor tyrosine kinases. Approximately 10–15% of patients with NSCLC have EGFR mutation ( ). Erlotinib, gefitinib, and afatinib are tyrosine kinase inhibitors (TKIs) that have activity against NSCLC with higher response rate and increased disease-free survival in EGFR mutation carriers as compared to conventional chemotherapy.

Brain metastases in EGFR-mutated NSCLC

reported that in an unselected 40 patients (non-Asian) with NSCLC with brain metastases, 50% of patients had EGFR mutation. Similarly, reported an EGFR mutation rate of 63% in patients with lung adenocarcinoma with brain metastases. These findings suggest that brain metastases occur more commonly in EGFR-mutated lung adenocarcinoma.