ALK抑制剂治疗克唑替尼耐药非小细胞肺癌有效性的Meta分析

目的:评价第二、三代ALK抑制剂治疗克唑替尼耐药后非小细胞肺癌（NSCLC）的临床疗效。方法:计算机检索PubMed、Cochrane library、Web of Science、中国知网、中国生物医学文献服务系统、维普数据库和万方数据库，收集关于第二、三代ALK抑制剂治疗克唑替尼耐药后晚期NSCLC的临床研究，检索时限为各数据库建库起至2020年7月26日。由两位研究者独立筛选文献、提取资料并进行交叉核对并评价纳入研究的偏倚风险后，采用Comprehensive Meta-analysis软件进行数据分析。结果:共纳入14项研究，2 036名受试者。Meta分析结果显示第二、三代ALK抑制剂治疗克唑替尼耐药NSCLC患者的客观缓解率（ORR）为0.520 ［95%CI(0.483,0.558)］，亚组分析中Loratinib的ORR显著高于Ceritinib(P＜0.05)；而Ensartinib的疾病控制率（DCR）显著高于Ceritinib、Alectinib、Brigatinib(P＜0.05)。对于存在颅内转移的患者，第二、三代ALK抑制剂的颅内客观缓解率（IORR）为0.515 ［95%CI(0.434,0.595)］，亚组分析中Ensartinib和Loratinib的IORR显著高于Certinib(P＜0.05)。颅内疾病控制率（IDCR）为0.834 ［95%CI(0.785,0.874)］，而Alectinib，Brigatinib和Ensartinib的IDCR显著高于Certinib(P＜0.05)。结论:本研究肯定了二代、三代ALK抑制剂对于克唑替尼治疗后的ALK阳性的NSCLC患者的治疗疗效。Ensartinib和Loratinib在总体治疗效果及颅内病灶控制方面显示出一定优势，但本研究纳入的研究数量有限，尚需要更多研究数据探索和分析予以验证上述结论。

The effects of ALK inhibitors in the treatment of patients with Crizotinib-resistant non-small-cell lung cancer(NSCLC):A single-arm Meta-analysis

Objective:To evaluate the clinical efficacy of the second and third generation ALK inhibitors in the treatment of ALK positive non-small cell lung cancer(NSCLC)after Crizotinib-resistant.Methods:The second and third generation ALK inhibitors in the treatment of advanced NSCLC after Crizotinib-resistant were searched through PubMed,Cochrane library,Web of Science,CNKI,SinoMed,VIP data and Wanfang database to collect the clinical trials.The search time ranged from inception to July 26,2020.After two independent researchers screened the literature,extracted the data,cross-checked and evaluated the risk of bias in the included studies,the data were analyzed by Comprehensive Meta-analysis software.Results:A total of 14 studies with 2 036 patients were included.The results of Meta analysis showed that the objective response rate(ORR)of the second and third generation ALK inhibitors in the treatment of NSCLC patients with Crizotinib-resistant was 0.520 ［95%CI(0.483,0.558)］,and subgroup analysis showed that the ORR of Loratinib was significantly higher than Ceritinib(P＜0.05).The disease control rate(DCR)of Certinib,Alectinib and Brigatinib was significantly lower than that of Ensartinib(P＜0.05).For patients with intracranial metastasis,the intracranial objective response rate(IORR)of the second and third generation ALK inhibitors was 0.515 ［95%CI(0.434,0.595)］.Subgroup analysis showed that the IORR of Ensartinib and Loratinib was significantly higher than Certinib(P＜0.05).The intracranial disease control rate(IDCR)was 0.834 ［95%CI(0.785,0.874)］and the IDCR of Alectinib,Brigatinib and Ensartinib was significantly higher than Certinib(P＜0.05).Conclusion:This study confirm the efficacy of second-and third-generation ALK inhibitors in the treatment of ALK-positive NSCLC patients treat with Crizotinib.Ensartinib and Loratinib show advantages in the overall therapeutic effect and the treatment of intracranial metastasis.Due to limitation of the included studies,more studies are needed to explore and analyze to verify the above conclusions.