康莱特联合吉非替尼治疗中晚期肺癌的Meta分析及试验序贯研究  

Kanglaite Combined with Gefitinib for Mid-Late Stage Lung Cancer:a Meta-Analysis and Trial Sequential Analysis

作　　者：范丽萍 鲁姝 蔡悦萍 万宇翔 孙慧媛 FAN Liping;LU Shu;CAI Yueping;WAN Yuxiang;SUN Huiyuan(Department of Pharmacy,Beijing University of Chinese Medicine Third Affiliated Hospital,Beijing 100029,China;Department of minimally invasive acupuncture Oncology,Beijing University of Chinese Medicine Third Affiliated Hospital,Beijing 100029,China;Internet Hospital Office,Beijing University of Chinese Medicine Third Affiliated Hospital,Beijing 100029,China)

机构地区：[1]北京中医药大学第三附属医院药学部,北京100029 [2]北京中医药大学第三附属医院针灸微创肿瘤科,北京100029 [3]北京中医药大学第三附属医院互联网诊疗办公室,北京100029

出　　处：《中国药物警戒》2025年第3期316-323,共8页Chinese Journal of Pharmacovigilance

基　　金：国家自然科学基金资助项目(82205292、82174203);第七批全国老中医药专家学术经验继承工作项目(国中医药人教函[2022]76号)。

摘　　要：目的系统评价康莱特联合吉非替尼治疗中晚期肺癌的有效性和安全性。方法检索从建库至2025年1月11日,Cochrane、PubMed、EMbase、Web of Science、中国知网、中国生物医学文献服务系统、万方数据以及维普网等中英文数据库中公开发表的关于康莱特联合吉非替尼治疗中晚期肺癌的随机对照试验(RCTs)。应用Cochrance协作网偏倚风险评价工具2.0版(ROB 2.0)对纳入文献进行偏倚风险评估,应用RevMan5.3软件进行Meta分析,应用Stata 12.0软件进行敏感性分析和Egger's检验,应用TSA 0.9.5.10 Beta软件进行试验序贯分析(TSA),应用GRADE对结局指标进行质量评价。结果最终纳入12项研究,合计1050例患者,ROB 2.0评估结果显示纳入研究均有一定偏倚风险。Meta分析结果显示,相较于单纯应用吉非替尼,康莱特联合吉非替尼治疗中晚期肺癌的疾病有效率[RR=1.66,95%CI(1.38,2.01),P<0.00001]和疾病控制率[RR=1.23,95%CI(1.11,1.37),P=0.0001];胃肠道不良反应[RR=0.68,95%CI(0.52,0.89),P=0.004];生活质量改善情况[按评分:MD=1.72,95%CI(1.27,2.34),P=0.000;按改善率:RR=7.66,95%CI(1.46,13.85),P=0.02]、CD3^(+)[MD=9.11,95%CI(3.37,14.85),P=0.002]、CD4^(+)[MD=4.83,95%CI(1.40,8.25),P=0.006]、CD4^(+)/CD8^(+)[MD=0.10,95%CI(0.06,0.14),P<0.00001]等T淋巴细胞亚群活性以及NK细胞活性[MD=4.26,95%CI(3.96,4.57),P<0.00001]等方面具有明显优势。亚组分析显示康莱特不同剂型影响疾病控制率的异质性。Egger's检验显示发表偏倚较小。TSA表明疾病有效率结果存在假阳性的可能,需要纳入更多高质量的RCTs对疗效加以验证。GRADE评价结果显示本研究的结局指标证据质量均较低。结论根据有限证据表明,康莱特联合吉非替尼在提高疗效、降低胃肠道不良反应、改善生活质量、提高免疫细胞活性方面优于对照组,未来需要更多RCTs来进一步开展有效性和安全性评价。Objective To evaluate the clinical efficacy and safety of kanglaite combined with gefitinib in the treatment of mid-late stage lung cancer.Methods Randomized controlled trials(RCTS)involving kanglaite combined with gefitinib in the treatment of mid-late stage lung cancer that were published between the inception and January 11,2025 were retrieved from Cochrane,PubMed,EMbase,Web of Science,CNKI,WANFANG and VIP database.Literature bias risk assessment was performed using the Cochrane Collaboration’s Risk of Bias 2.0 tool(ROB 2.0).RevMan 5.3 software was used for Meta-analysis.STATA12.0 software was used for sensitivity analysis and Egger's test.TSA 0.9.5.10 beta software was used for the trial sequential analysis(TSA).GRADE was used for quality evaluation of outcome indicators.Results Twelve trials involving 1050 patients were included.ROB 2.0 results of all the studies included revealed some concerns.The results of Meta-analysis showed that the combination of Kanglaite and gefitinib in the treatment of mid-late stage lung cancer had significant advantages over gefitinib alone in clinical efficacy.Subgroup analysis showed that different dosage forms of kanglaite affected the heterogeneity of the disease control rate.Egger's test exhibited less publication bias.TSA indicated the possibility of false-positive results in the disease response rate,and more high-quality RCTs were needed to validate the efficacy.The results of the GRADE evaluation showed that the evidence quality of the outcome indicators in this study was low or exceedingly low.Conclusion Kanglaite combined with gefitinib in the treatment of advanced lung cancer is superior to the control group in improving efficacy,reducing gastrointestinal adverse reactions,improving quality of life,and the activity of immune cells,but more randomized controlled trials are needed for efficacy and safety evaluations.

关 键 词：康莱特 吉非替尼 中晚期肺癌 META分析 试验序贯分析 

分 类 号：R979.1[医药卫生—药品] R994.11[医药卫生—药学]