Tang Hao, Jin Longyu, Zhang Zhang, Jiang Zhibin, Malik Zeeshan
Department of Cardio-Thoracic Surgery, The Third Xiangya Hospital, Central South University, Changsha, China.
Department of Cardio-Thoracic Surgery, Changsha Central Hospital, Changsha, China.
Front Oncol. 2021 Jun 2;11:646526. doi: 10.3389/fonc.2021.646526. eCollection 2021.
To systematically evaluate the efficacy and safety of alectinib versus crizotinib in the treatment of anaplastic lymphoma kinase () positive non-small-cell lung cancer.
Studies about the efficacy of alectinib versus crizotinib in the treatment of -positive non-small cell lung cancer were searched in PubMed, Scopus, Embase and the Cocharane Library from inception to February 15, 2020. Two reviewers independently screened these studies, extracted the data, assessed the risk of bias in the included studies by using the Cochrane risk assessment tool, and then used review manager 5.3 software for meta-analysis.
Three studies comprising a total of 697 patients with -positive non-small cell lung cancer were included, 380 in the alectinib group and 317 in the crizotinib group. The dose of alectinib (300 mg) in J-ALEX were lower than the approved dose (600 mg), however the crizotinib group in all three studies received the recommended dose (250 mg). Performance bias was high in all three studies whereas, and the attrition bias was high in two studies (Toyoaki Hida 2017 and Solange peters 2017). The results of meta-analysis showed that: the overall response rate [OR = 2.07, 95% CI (1.41, 3.06), P = 0.0002], the progression free survival [HR = 0.34, 95% CI (0.21, 0.55), P <0.0001], the partial response [OR = 1.71, 95% CI (1.19, 2.46), P = 0.003], P = 0.001], in alectinib group were higher than that of crizotinib group. Though the total number of events in complete response and the disease control rate were more in alectinib group than that of crizotinib group, the meta-analysis results shows no significant differences between two drugs in the disease control rate [OR = 2.24, 95% CI (0.56, 8.88), P = 0.25], the complete response [OR = 1.82, 95% CI (0.75, 4.45), P = 0.19]. In addition, the number of events in the stable disease [OR = 0.45, 95% CI (0.28, O.74), P = 0.001], and the adverse events [OR = 0.50, 95% CI (0.23, 0.81), P = <0.0001] in alectinib group were lower than that of crizotinib group.
Alectinib in terms of overall response rate, progression-free survival and partial response is superior to crizotinib in the treatment of -positive non-small cell lung cancer and is well tolerated. Compared with crizotinib, alectinib is more effective than crizotinib and has a lower incidence of total adverse reactions. Meta-analysis results confirm the strong base for alectinib as a first-line treatment for -positive NSCLC.
系统评价阿来替尼与克唑替尼治疗间变性淋巴瘤激酶(ALK)阳性非小细胞肺癌的疗效和安全性。
在PubMed、Scopus、Embase和Cochrane图书馆中检索从创刊至2020年2月15日关于阿来替尼与克唑替尼治疗ALK阳性非小细胞肺癌疗效的研究。两名评价员独立筛选这些研究,提取数据,使用Cochrane风险评估工具评估纳入研究的偏倚风险,然后使用Review Manager 5.3软件进行荟萃分析。
纳入3项研究,共697例ALK阳性非小细胞肺癌患者,阿来替尼组380例,克唑替尼组317例。J-ALEX研究中阿来替尼的剂量(300mg)低于批准剂量(600mg),但三项研究中克唑替尼组均接受推荐剂量(250mg)。三项研究中的表现性偏倚均较高,两项研究(Toyoaki Hida 2017和Solange peters 2017)中的损耗性偏倚较高。荟萃分析结果显示:阿来替尼组的总缓解率[比值比(OR)=2.07,95%置信区间(CI)(1.41,3.06),P=0.0002]、无进展生存期[风险比(HR)=0.34,95%CI(0.21,0.55),P<0.0001]、部分缓解率[OR=1.71,95%CI(1.19,2.46),P=0.003]均高于克唑替尼组。虽然阿来替尼组完全缓解的事件总数和疾病控制率高于克唑替尼组,但荟萃分析结果显示两种药物在疾病控制率[OR=2.24,95%CI(0.56,8.88),P=0.25]、完全缓解率[OR=1.82,95%CI(0.75,4.45),P=0.19]方面无显著差异。此外,阿来替尼组疾病稳定的事件数[OR=0.45,95%CI(0.28,0.74),P=0.001]和不良事件数[OR=0.50,95%CI(0.23,0.81),P<0.0001]低于克唑替尼组。
在治疗ALK阳性非小细胞肺癌方面,阿来替尼在总缓解率、无进展生存期和部分缓解率方面优于克唑替尼,且耐受性良好。与克唑替尼相比,阿来替尼疗效更佳,总不良反应发生率更低。荟萃分析结果证实了阿来替尼作为ALK阳性非小细胞肺癌一线治疗药物的有力依据。