EGFR-TKI therapy for patients with brain metastases from non-small-cell lung cancer: a pooled analysis of published data
EGFR-TKI therapy for patients with brain metastases from non-small-cell lung cancer: a pooled analysis of published data
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DOI：
10.2147/ott.s67586
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发表时间：
2014-01-01
影响因子：
4
通讯作者：
Xie, Conghua
中科院分区：
文献类型：
--
作者：
Fan, Yun;Xu, Xiaoling;Xie, Conghua
前言：脑转移是非小细胞肺癌(NSCLC)的主要死亡原因之一。使用表皮生长因子受体(EGFR)酪氨酸激酶抑制剂(TKIs)治疗脑转移瘤仍存在争议。因此，我们对已发表的数据进行了综合分析，以评估EGFR-TKIs对脑转移患者的疗效，特别是对激活EGFR突变的肿瘤患者的疗效。方法：搜索几个数据来源，包括PubMed、Web of Science和ASCO年会数据库。终点为颅内总有效率(ORR)、疾病控制率(DCR)、无进展生存期(PFS)、总生存期(OS)和不良事件。根据纳入研究的异质性，采用固定或随机效应模型计算合并ORR、DCR、PFS和OS的95%可信区间(CI)。结果：16项已发表的研究纳入本分析，共有464名入选患者。362例(未选择组)的EGFR突变状态未知，102例有激活的EGFR突变。合并后的颅内ORR为51.8%(95%CI：45.8%~57.8%)，DCR为75.7%(95%CI：70.3%~80.5%)。EGFR突变组ORR(85.0%)高于未选择组(45.1%)；DCR组ORR(94.6%)高于未选择组(71.3%)。EGFR基因突变组的中位生存期为7.4个月(95%CI，4.9~9.9个月)，OS为11.9个月(95%CI，7.7~16.2个月)，其中PFS(12.3个月vs 5.9个月)和OS(16.2个月vs 10.3个月)均长于未选择组。结论：EGFR-TKIs治疗NSCLC脑转移瘤是一种有效的治疗方法。有必要进行更大规模的前瞻性随机临床试验，以证实我们的结论并确定最合适的治疗模式。
Introduction: Brain metastases are one of the leading causes of death from non-small-cell lung cancer (NSCLC). The use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) to treat brain metastases remains controversial. Thus, we performed a pooled analysis of published data to evaluate the efficacy of EGFR-TKIs in NSCLC patients with brain metastases, particularly for tumors with activating EGFR mutations.Methods: Several data sources were searched, including PubMed, Web of Science, and ASCO Annual Meetings databases. The end points were intracranial overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events. The pooled ORR, DCR, PFS, and OS with 95% confidence intervals (CIs) were calculated employing fixed- or random-effect models, depending on the heterogeneity of the included studies.Results: Sixteen published studies were included in this analysis, with a total of 464 enrolled patients. The EGFR mutational status was unknown for 362 (unselected group), and 102 had activating EGFR mutations. The pooled intracranial ORR and DCR were 51.8% (95% CI: 45.8%-57.8%) and 75.7% (95% CI: 70.3%-80.5%), respectively. A higher ORR was observed in the EGFR mutation group than in the unselected group (85.0% vs 45.1%); a similar trend was observed for the DCR (94.6% vs 71.3%). The pooled median PFS and OS were 7.4 months (95% CI, 4.9-9.9) and 11.9 months (95% CI, 7.7-16.2), respectively, with longer PFS (12.3 months vs 5.9 months) and OS (16.2 months vs 10.3 months) in the EGFR mutation group than in the unselected group.Conclusion: This pooled analysis strongly suggests that EGFR-TKIs are an effective treatment for NSCLC patients with brain metastases, particularly in those patients harboring EGFR mutations. Larger prospective randomized clinical trials are warranted to confirm our conclusion and identify the most appropriate treatment model.