The incidence of brain metastases from lung cancer accounts for 40%-60% of brain metastases from solid tumors, and its biological behavior is aggressive with poor prognosis. Chemotherapy has been secondary in the treatment of brain metastases, but some new drugs and molecularly targeted drugs have emerged in recent years to show some efficacy. The efficacy of chemotherapy temozolomide (TMZ) in glioma has been demonstrated, and it has also shown initial efficacy in brain metastases such as lung cancer. In a phase II study, the objective remission rate (ORR) of TMZ monotherapy was 10% in 30 patients with brain metastases from non-small cell lung cancer (NSCLC), and the time to disease progression (TTP) and overall survival (OS) of patients in remission ranged from 11 to 19 months and 14 to 24 months, respectively. In another phase II study, patients with relapsed refractory NSCLC treated with low-dose TMZ (39% of whom had combined brain metastases) had a disease control rate (DCR) of 16.2%, with TTP and OS of 2.4 months and 3.3 months, respectively. A phase II study showed that TMZ combined with cisplatin sequential whole brain radiotherapy in 50 patients with NSCLC brain metastases had an ORR of 16% and a TTP and OS of 2.3 and 5 months, respectively. In contrast, two other phase II studies showed that the ORR of TMZ with concurrent radiotherapy was 45%-58% and OS was 12-13 months, indicating that concurrent radiotherapy may be superior to sequential radiotherapy or single chemotherapy. In addition, a study showed that only 8% of patients treated with TMZ in combination with topotecan eventually developed brain metastases, which is much lower than the 50% reported in the literature, suggesting that TMZ may have a role in preventing brain metastases. Targeted therapy Currently, several studies have confirmed the effectiveness of tyrosine kinase inhibitors (TKI) for the treatment of brain metastases from lung cancer, among which gefitinib has been studied more frequently. In a retrospective study in Japan, of 14 NSCLC patients with intracranial and extracranial metastases treated with gefitinib, six achieved remission of intracranial lesions. In a prospective phase II study, gefitinib treated 41 patients with NSCLC brain metastases had an ORR of 10% and median progression-free survival (PFS) and OS of 3 and 5 months, respectively, with relatively long survival in patients with adenocarcinoma (P=0.04). Another prospective study in China included 40 patients screened for brain metastases from lung adenocarcinoma, and the efficiency of gefitinib treatment was 38%, DCR was 92%, symptoms improved or disappeared in 48%, median PFS was 9 months, median OS was 15 months, and the incidence of rash was 100%, but mostly grade 1-2. This study showed that gefitinib was more effective than unscreened patients with brain metastases. Several retrospective analyses also showed that gefitinib treatment was more effective in patients with rash and EGFR mutations. Thus, the clinical benefit of TKI treatment may be more pronounced in patients with EGFR mutations or brain metastases with specific clinical features.