Role of EGFR Inhibitors in the Treatment of Central Nervous System Metastases from Non-Small Cell Lung Cancer

Brain metastases (BM) are a common occurrence in patients with non-small cell lung cancer (NSCLC). Standard therapy options include whole brain radiotherapy and, in selected patients, surgery or stereotactic radiosurgery. The role of systemic treatment is controversial. There is a strong clinical rationale for the use of targeted therapies, because patients often have a poor performance status, and are not candidates for cytotoxic chemotherapy or radiotherapy, yet treatment is required to improve the extra-cranial disease. The efficacy of epidermal growth factor receptor (EGFR) inhibitors in the treatment of patients with BM from NSCLC has been reported mainly in case reports or small retrospective case series, with only a few prospective trials. Current evidence suggests that the use of EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib should be considered in patients with asymptomatic CNS involvement, when clinical characteristics suggest a high likelihood of response; these characteristics are adenocarcinoma histology, never-smoker status, female gender and East Asian ethnicity. Upfront therapy with EGFR TKIs should be strongly considered in asymptomatic patients harboring activating EGFR mutations. In symptomatic BM, radiotherapy (RT) remains the standard treatment. Based on currently available data, treatment with concurrent RT and EGFR TKIs should be investigated in experimental trials only.