劳拉替尼治疗非小细胞肺癌临床疗效的Meta分析及其安全性评价  

Meta-Analysis and Safety Evaluation on Clinical Efficacy of Lorlatinib in the Treatment of Non-Small Cell Lung Cancer

作　　者：王青 赵璐 吴尚 刘夏铭 曹璐 WANG Qing;ZHAO Lu;WU Shang;LIU Xiaming;CAO Lu(Dept.of Pharmacy,Children’s Hospital of Nanjing Medical University,Nanjing 210008,China;College of Life Science,Zhejiang Chinese Medical University,Hangzhou 310053,China;Dept.of Urology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China)

机构地区：[1]南京医科大学附属儿童医院药学部,南京210008 [2]浙江中医药大学生命科学学院,杭州310053 [3]华中科技大学同济医学院附属同济医院泌尿外科,武汉430030

出　　处：《中国医院用药评价与分析》2023年第2期212-218,共7页Evaluation and Analysis of Drug-use in Hospitals of China

基　　金：国家自然科学基金项目(No.82072838);浙江省大学生科技创新活动计划暨新苗人才计划立项项目(No.2022R410A038)。

摘　　要：目的:基于Meta分析方法,评价劳拉替尼治疗非小细胞肺癌(NSCLC)的临床疗效,并探讨劳拉替尼致药品不良反应(ADR)的临床表现、特点、规律及转归,为临床安全用药提供参考。方法:检索中国知网、万方数据库、PubMed和Web of Science等数据库,纳入关于劳拉替尼治疗NSCLC的随机对照试验[劳拉替尼组患者在有或无用药基础上采用劳拉替尼治疗方案,对照组患者采用第1代和(或)第2代间变性淋巴瘤激酶(ALK)-酪氨酸激酶抑制剂(TKI)治疗方案]进行Meta分析,并纳入劳拉替尼致ADR的文献进行分析。结果:共纳入5项符合条件的随机对照试验,包含622例患者(劳拉替尼组308例,对照组314例),以客观缓解率(ORR)为主要结局指标。Meta分析结果显示,劳拉替尼组患者ORR明显优于对照组,差异有统计学意义(OR=2.31,95%CI=1.62~3.28,P<0.00001),表明劳拉替尼的疗效较前2代药物显著。同时收集到劳拉替尼所致ADR 14例,其中男性患者6例,女性患者8例;>60~70岁年龄段患者较多,共7例;大多数ADR发生在用药2周后,主要涉及呼吸系统及心血管系统损害;所有的ADR经停药和(或)对症支持治疗后,症状好转或改善;2例经停药或减量再次使用后症状再现。结论:作为第3代治疗NSCLC的ALK-TKI,劳拉替尼治疗NSCLC的水平显著提高。但是,临床上使用劳拉替尼时需严格监控胆固醇和三酰甘油水平,同时在用药早期需警惕中枢神经系统损害及交叉不良反应的发生。OBJECTIVE:To evaluate the clinical efficacy of lorlatinib in the treatment of non-small cell lung cancer(NSCLC)based on Meta-analysis method,and to probe into the clinical manifestations,characteristics,patterns and outcomes of adverse drug reactions(ADR)induced by lorlatinib,so as to provide references for the clinical safe medication.METHODS:By retrieving CNKI,Wanfang Data,PubMed,Web of Science and other database,randomized controlled trials(RCT)on lorlatinib in the treatment of NSCLC[the lorlatinib group was given lorlatinib regimen with or without other medication,and the control group was given the first and(or)the second generation of anaplastic lymphoma kinase(ALK)-tyrosine kinase inhibitor(TKI)regimen]were enrolled for Meta-analysis,and studies on ADR induced by lorlatinib were also analyzed.RESULTS:Totally 5 eligible RCT were enrolled,including 622 patients(308 cases in the lorlatinib group,314 cases in the control group),the objective remission rate(ORR)was used as the main outcome indicator.The results of Meta-analysis showed that the ORR of the lorlatinib group was higher than that of the control group,with statistically significant difference(OR=2.31,95%CI=1.62-3.28,P<0.00001),which indicated that the efficacy of lorlatinib was significant compared with the previous 2 generations of drugs.Fourteen cases of ADR induced by lorlatinib were also collected,including 6 male patients and 8 female patients;there were more patients in the age group of>60 to 70 years old,with 7 cases;most ADR occurred at 2 weeks after medication,mainly involved cardiovascular system damage and respiratory system damage;all ADR were improved after drug withdrawal and(or)symptomatic supportive treatment;2 cases showed no improvement or aggravation of symptoms at recurrence.CONCLUSIONS:As the third generation of ALK-TKI to treat NSCLC,the level of loratinib to treat NSCLC was significantly improved.However,clinical application of lorlatinib requires strict monitoring on cholesterol and triacylglycerol levels,as well as vigilance

关 键 词：劳拉替尼 非小细胞肺癌 META分析 药品不良反应 药物安全性评价 

分 类 号：R979.1[医药卫生—药品]