Chapter 14 – Brain Metastases from Non-Small Cell Lung Cancer: Clinical Benefits of Erlotinib and Gefitinib

Brain metastases are seen in a considerable number of patients with non-small cell lung cancer (NSCLC) and when they occur will pose a negative impact on patients’ survival. Diverse therapeutic options are being used to treat brain metastases including surgical excision, stereotactic radiosurgery, whole brain radiotherapy and systemic therapy. Of systemic therapies, gefitinib and erlotinib, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), have shown benefit in treatment of brain metastases in patients with NSCLC. They are particularly effective in those whose lesions harbor activating EGFR mutations, as well as those selected with certain clinical features including young non-smokers, females, and those with East-Asian ethnicity or with adenocarcinoma histology. Gefitinib and erlotinib also have the advantage of exerting their antitumor activity with a favorable toxicity profile. However, they may fail after months of continuous use due to development of drug resistance. In these situations, adopting other treatment strategies such as switching drugs or dose escalation may be suitable alternatives. Several clinical trials in different phases are currently evaluating the efficacy of gefitinib or erlotinib in larger populations of NSCLC patients with brain metastases. On the other hand, new drugs such as afatinib, icotinibor crizotinib have shown benefit in patients with corresponding molecular alterations, at least in case reports or in early phase trials, and are awaiting further study in larger populations.