Kai Dong1, Wenhua Liang2,3, Shen Zhao4, Minzhang Guo2,3, Qihua He2,3, Caichen Li2,3, Haiqing Song1, Jianxing He2,3, Xiaojun Xia2,3. 1. Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100000, China. 2. Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China. 3. State Key Laboratory of Respiratory Disease & National Clinical Research Center of Respiratory Disease, Guangzhou 510120, China. 4. Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
Abstract
BACKGROUND: It has been confirmed that epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) presented better efficacy than brain radiotherapy (brain RT) in the treatment of brain metastasis (BM) in EGFR mutated NSCLC patients. However, whether the combination of EGFR-TKIs and brain RT is better than EGFR-TKIs alone remains unclear. We aim to compare the outcomes of adding brain RT to EGFR-TKIs and to screen for the beneficial population by a meta-analysis of currently available data. METHODS: A systematic search for relevant articles was conducted in six databases. The outcomes were overall survival (OS) and intracranial progression-free survival (iPFS) between groups, both were measured as hazard ratios (HRs). Meta-regression and dominant subgroup analysis were used to explore advantageous subgroups. RESULTS: A total of 12 retrospective studies involving 1,553 EGFR mutated patients with BM at the first diagnosis were included. EGFR-TKIs plus brain RT showed a significant prolonged OS (HR =0.64, 95% CI: 0.52-0.78; P<0.001) and iPFS (HR =0.62, 95% CI: 0.50-0.78; P<0.001) compared to EGFR-TKIs alone. Meta-regression analyses showed that potential factors contributed to the heterogeneity were the proportion of ECOG performance score (2+ vs. 0-1, P=0.070) and brain symptomatic patients (no vs. yes, P=0.077) regarding iPFS and was age (younger vs. older, P=0.075) for OS. Dominant subgroup analyses suggested that symptomatic patients (HR 0.46 vs. 0.74, interaction P=0.01) for iPFS, and older patients (HR 0.55 vs. 0.75, interaction P=0.03) and 19Del mutation (HR 0.55 vs. 0.74, interaction P=0.04) for OS, seemed to benefit more from the combination therapy than their counterparts. However, direct subgroup results based on only two studies did not show significant difference in iPFS benefit between age, mutation type and sex subgroup. CONCLUSIONS: EGFR-TKIs plus brain RT is superior to EGFR-TKIs alone in the management of EGFR-mutated NSCLC patients with BM, of which the benefits might be influenced by age, BM-related symptoms and mutation type.
BACKGROUND: It has been confirmed that epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) presented better efficacy than brain radiotherapy (brain RT) in the treatment of brain metastasis (BM) in EGFR mutated NSCLC patients. However, whether the combination of EGFR-TKIs and brain RT is better than EGFR-TKIs alone remains unclear. We aim to compare the outcomes of adding brain RT to EGFR-TKIs and to screen for the beneficial population by a meta-analysis of currently available data. METHODS: A systematic search for relevant articles was conducted in six databases. The outcomes were overall survival (OS) and intracranial progression-free survival (iPFS) between groups, both were measured as hazard ratios (HRs). Meta-regression and dominant subgroup analysis were used to explore advantageous subgroups. RESULTS: A total of 12 retrospective studies involving 1,553 EGFR mutated patients with BM at the first diagnosis were included. EGFR-TKIs plus brain RT showed a significant prolonged OS (HR =0.64, 95% CI: 0.52-0.78; P<0.001) and iPFS (HR =0.62, 95% CI: 0.50-0.78; P<0.001) compared to EGFR-TKIs alone. Meta-regression analyses showed that potential factors contributed to the heterogeneity were the proportion of ECOG performance score (2+ vs. 0-1, P=0.070) and brain symptomatic patients (no vs. yes, P=0.077) regarding iPFS and was age (younger vs. older, P=0.075) for OS. Dominant subgroup analyses suggested that symptomatic patients (HR 0.46 vs. 0.74, interaction P=0.01) for iPFS, and older patients (HR 0.55 vs. 0.75, interaction P=0.03) and 19Del mutation (HR 0.55 vs. 0.74, interaction P=0.04) for OS, seemed to benefit more from the combination therapy than their counterparts. However, direct subgroup results based on only two studies did not show significant difference in iPFS benefit between age, mutation type and sex subgroup. CONCLUSIONS: EGFR-TKIs plus brain RT is superior to EGFR-TKIs alone in the management of EGFR-mutated NSCLC patients with BM, of which the benefits might be influenced by age, BM-related symptoms and mutation type.
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