Research Progress on Brain Metastases to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in EGFR-mutated Non-small Cell Lung Cancer Patients

Brain metastases(BM) complicate clinical evolution of non-small cell lung cancer (NSCLC) in approximately 30%-50% of cases, adversely influencing quality of life(QOL) and overall survival (OS). Systemic therapy remains the standard strategy for metastatic disease. To date, the combination of chemotherapy with whole brain radiation therapy(WBRT), surgery or stereotactic radiosurgery(SRS) represent the most common treatments for BM patients. Therapies targeting epidermal growth factor receptor(EGFR), such as gefitinib, erlotinib and icotinib, achieve important improvements in EGFR-mutated NSCLC with favorable toxicity profile. The incidence of adverse reactions in icotinib is lower, the clinical use is safer, and the advantage is more pronounced when increasing the dose. The reported objective response rate (ORR), well safety and tolerance make EGFR-tyrosine kinase inhibitors(TKIs) an interesting valid alternative for NSCLC patients with BM, especially for those harboring EGFR mutations. Furthermore, new-generation TKIs, such as AZD9291 and AZD3759, have already shown important activity on intracranial disease and several trials are still ongoing to evaluate their efficacy. In this review, we want to highlight literature data about the use and the effectiveness of EGFR-TKIs on patients with BM from EGFR-mutated NSCLC.