表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）联合脑部放疗与单纯EGFR-TKI治疗表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）脑转移患者的疗效比较
EGFR-TKI plus brain radiotherapy versus EGFR-TKI alone in the management of EGFR-mutated NSCLC patients with brain metastases.
作者信息
Dong Kai, Liang Wenhua, Zhao Shen, Guo Minzhang, He Qihua, Li Caichen, Song Haiqing, He Jianxing, Xia Xiaojun
机构信息
Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100000, China.
Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
出版信息
Transl Lung Cancer Res. 2019 Jun;8(3):268-279. doi: 10.21037/tlcr.2019.06.12.
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+ . 0-1, P=0.070) and brain symptomatic patients (no . yes, P=0.077) regarding iPFS and was age (younger . older, P=0.075) for OS. Dominant subgroup analyses suggested that symptomatic patients (HR 0.46 . 0.74, interaction P=0.01) for iPFS, and older patients (HR 0.55 . 0.75, interaction P=0.03) and 19Del mutation (HR 0.55 . 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.
背景
已证实表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）在治疗EGFR突变的非小细胞肺癌（NSCLC）患者脑转移（BM）方面比脑放射治疗（脑RT）具有更好的疗效。然而，EGFR-TKIs与脑RT联合使用是否优于单独使用EGFR-TKIs仍不清楚。我们旨在通过对现有数据进行荟萃分析，比较在EGFR-TKIs基础上加用脑RT的疗效，并筛选出受益人群。
方法
在六个数据库中系统检索相关文章。结局指标为两组之间的总生存期（OS）和颅内无进展生存期（iPFS），均以风险比（HRs）衡量。采用荟萃回归和优势亚组分析来探索优势亚组。
结果
共纳入12项回顾性研究，涉及1553例初诊为EGFR突变的BM患者。与单独使用EGFR-TKIs相比，EGFR-TKIs联合脑RT显示OS（HR =0.64，95%CI：0.52-0.78；P<0.001）和iPFS（HR =0.62，95%CI：0.50-0.78；P<0.001）显著延长。荟萃回归分析显示导致异质性的潜在因素，对于iPFS是ECOG体能状态评分的比例（2+对0-1，P=0.070）和有脑症状的患者（无对有，P=0.077），对于OS是年龄（年轻对年长，P=0.075）。优势亚组分析表明，有症状的患者对于iPFS（HR 0.46对0.74，交互作用P=0.01），以及老年患者对于OS（HR 0.55对0.75，交互作用P=0.03）和19Del突变对于OS（HR 0.55对0.74，交互作用P=0.04），似乎从联合治疗中获益更多。然而，仅基于两项研究的直接亚组结果未显示年龄、突变类型和性别亚组在iPFS获益方面有显著差异。
结论
在治疗EGFR突变的NSCLC合并BM患者中，EGFR-TKIs联合脑RT优于单独使用EGFR-TKIs，其获益可能受年龄、BM相关症状和突变类型影响。
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