克唑替尼单药治疗ALK阳性非小细胞肺癌患者严重不良事件和致命不良事件的发生率及风险的荟萃分析。
Meta-analysis of incidence and risk of severe adverse events and fatal adverse events with crizotinib monotherapy in patients with -positive NSCLC.
作者信息
Zhu Qian, Hu Hao, Jiang Feng, Guo Chang Ying, Yang Xiong Wen, Liu Xi, Kuang Yu Kang
机构信息
Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong, China.
Department of Thoracic Surgery, Medical College of Nanchang University, Nanchang 330000, Jiangxi, China.
出版信息
Oncotarget. 2017 Jun 17;8(43):75372-75380. doi: 10.18632/oncotarget.18536. eCollection 2017 Sep 26.
BACKGROUND
Numerous clinical trials show crizotinib has promising efficacy for anaplastic lymphoma kinase () positive non-small cell lung cancer (NSCLC) patients which trigger the substitution of traditional chemotherapy to be the current standard first-line treatment for these patients. Conversely, few reports systematically analyze toxicity of crizotinib. Hence, we performed a first meta-analysis to determine the risk of crizotinib-related severe adverse events (SAEs) and fatal adverse events (FAEs) in positive NSCLC patients.
MATERIALS AND METHODS
A systematic literature search was conducted through December 2016 to identify clinical trials that reported crizotinib monotherapy in ALK-positive NSCLC patients. Data on crizotinib-related SAEs and FAEs were extracted from each study and pooled to determine the overall incidence and risk. Random-effects or fixed-effects models were conducted to calculate the summary incidence, relative risk (RR), and 95% CIs on basis of the heterogeneity of included studies.
RESULTS
1,924 patients from 11 clinical trials were included. The overall incidence of SAEs and FAEs with crizotinib was 19.9% (95% CI, 14.1% to 23.7%; < 0.001) and 1.4% (95% CI, 0.9% to 2.1%; < 0.001), respectively. Meanwhile, Asian patients have lower incidence of SAEs (11.5%, 95% CI: 7.9% to 16.5%). However, significant differences of SAEs (RR: 0.97, 95% CI, 0.79 to 1.18; = 0.76) and FAEs (RR: 2.24, 95% CI, 0.49 to 10.30; = 0.30) were not detected between crizotinib monotherapy and chemotherapy.
CONCLUSIONS
Crizotinib may not increase the risk of SAEs and FAEs in patients with positive NSCLC compared with chemotherapy.
背景
众多临床试验表明，克唑替尼对间变性淋巴瘤激酶（ALK）阳性非小细胞肺癌（NSCLC）患者具有显著疗效，这促使其取代传统化疗成为此类患者当前的标准一线治疗方案。相反，鲜有报道系统分析克唑替尼的毒性。因此，我们开展了首例荟萃分析，以确定ALK阳性NSCLC患者中与克唑替尼相关的严重不良事件（SAEs）和致命不良事件（FAEs）的风险。
材料与方法
通过检索截至2016年12月的文献，以确定报告克唑替尼单药治疗ALK阳性NSCLC患者的临床试验。从每项研究中提取与克唑替尼相关的SAEs和FAEs数据，并进行汇总以确定总体发生率和风险。根据纳入研究的异质性，采用随机效应或固定效应模型计算汇总发生率、相对风险（RR）和95%置信区间（CIs）。
结果
纳入了来自11项临床试验的1924例患者。克唑替尼治疗的SAEs和FAEs总体发生率分别为19.9%（95%CI，14.1%至23.7%；P<0.001）和1.4%（95%CI，0.9%至2.1%；P<0.001）。同时，亚洲患者的SAEs发生率较低（11.5%，95%CI：7.9%至16.5%）。然而，在克唑替尼单药治疗与化疗之间，未检测到SAEs（RR：0.97，95%CI，0.79至1.18；P = 0.76）和FAEs（RR：2.24，95%CI，0.49至10.30；P = 0.30）的显著差异。
结论
与化疗相比，克唑替尼可能不会增加ALK阳性NSCLC患者发生SAEs和FAEs的风险。
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