第二代ALK抑制剂治疗ALK^+非小细胞肺癌有效性单组率的Meta分析

The effects of ceritinib and alectinib on ALK-rearrangement non-small-cell lung cancer(NSCLC):a single-arm meta-analysis

目的系统评价第二代ALK抑制剂(色瑞替尼和艾洛替尼)治疗ALK^+非小细胞肺癌的疗效及颅内病灶控制效果。方法计算机检索Pub Med、EMbase、The Cochrane Library、Clinical Trials.gov、Wan Fang Data和VIP数据库,搜集色瑞替尼或艾洛替尼治疗ALK+非小细胞肺癌的临床研究,检索时限为建库至2017年12月31日。由2位评价员独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用Stata 12.0软件进行Meta分析。结果共纳入11个研究。Meta分析结果显示:色瑞替尼和艾洛替尼治疗非小细胞肺癌的客观缓解率(ORR)为57%[95%CI(0.48,0.66),P<0.001];对于克唑替尼耐药患者,ORR为51%[95%CI(0.44,0.57),P<0.001];对于存在脑转移的患者,其颅内病灶控制率(IDCR)为78%[95%CI(0.71,0.86),P<0.001]。结论第二代ALK抑制剂显示出明显的抗肿瘤效果。受纳入研究质量和数量限制,上述结论仍需更多大样本、高质量研究予以验证。

Objectives To systematically evaluate the effects of second-generation ALK-inhibitors： Ceritinib and Alectinib on ALK＋ NSCLC patients. Methods PubMed, EMbase, The Cochrane Library, WanFang Data, ClinicalTrials.gov and VIP databases were systematically searched for clinical trials containing treatment of two principal second-generation ALK-inhibitors for ALK （＋） NSCLC patients from inception to December 31^st, 2017. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias included in the studies. Stata 12.0 software was used for meta-analysis. Results Eleven studies were included. Meta-analysis showed that the ORR of all was 57% （95%CI 0.48 to 0.66, P〈0.001）. The ORR of patients with Crizotinib-resistance was 51% （95%CI 0.44 to 0.57, P〈0.001）. The IDCR of patients who had brain metastases was 78% （95%CI 0.71 to 0.86, P〈0.001）. Conclusions The second-generation ALK-inhibitors has effect on ALK （＋） NSCLC. Due to limitation of the included studies, more larger sample studies are required to verify above conclusions.