卡瑞利珠联合化疗治疗非小细胞肺癌的有效性及安全性Meta分析

A Meta-analysis of the Efficacy and Safety of Camrelizumab Combined with Chemotherapy in the Treatment of Non-small Cell Lung Cancer

目的讨论免疫检查点抑制剂卡瑞利珠单独用药与联合化疗治疗非小细胞肺癌的疗效差异以及安全性,综合多个临床试验数据进行聚合分析,得到更准确的疗效及安全性评价。方法通过检索PubMed、Embase、Cochrane Library、CBM数据库、中国知网、维普中文数据库和万方数据库,收集建库至2023年11月30日发表的符合要求的随机化对照试验或非随机对照实验,提取数据后应用Revman5.4软件进行数据分析。按照治疗方案的不同,将研究对象分为卡瑞利珠联合化疗组和单独化疗组进行研究讨论。结果共纳入19篇文献,共计1545名患者。Meta分析结果显示:与单纯化疗相比,卡瑞利珠联合化疗治疗非小细胞肺癌能更有效的提高治疗总体有效率(OR=2.50,95%CI:2.02~3.08,P<0.00001),提高CD4^(+)/CD8^(+)比值(MD=0.26,95%CI:0.19~0.33,P<0.00001)以及有效降低血清肿瘤标志物CA125(MD=-10.65,95%CI:-14.34~-6.96,P<0.00001)、CEA(MD=-5.56,95%CI:-7.64~-3.47,P<0.00001)、CY211(MD=-2.17,95%CI:-3.22~-1.13,P<0.00001)。不同不良反应表现不同聚类分析结果,其中卡瑞利珠联合化疗组相较于单独化疗组会增加贫血(OR=1.95,95%CI:1.09~3.51,P=0.03)、甲减(OR=5.61,95%CI:1.82~17.25,P=0.003)、毛细血管增多症(OR=2.86,95%CI:1.19~6.88,P=0.02)等症状的发生比例,差异有统计学意义(P<0.05);但是皮疹(OR=1.34,95%CI:0.82~2.16,P=0.24)、骨髓抑制(OR=1.06,95%CI:0.56~2.02,P=0.86)、白细胞减少(OR=0.78,95%CI:0.40~1.52,P=0.47)、脱发(OR=1.29,95%CI:0.57~2.92,P=0.54)、神经异常(OR=1.17,95%CI:0.39~3.56,P=0.78)、消化道异常(OR=1.10,95%CI:0.79~1.53,P=0.57)、肝功异常(OR=1.54,95%CI:0.92~2.59,P=0.10)、恶心呕吐(OR=1.16,95%CI:0.58~2.31,P=0.67)、咳血(OR=0.87,95%CI:0.30~2.49,P=0.79)、发热(OR=1.22,95%CI:0.65~2.30,P=0.54)及其他症状(OR=1.32,95%CI:0.76~2.31,P=0.32)的发生率没有明显变化,差异无统计学意义(P>0.05)。综合上述各类不良反应发生率,从总体上看,卡瑞利珠联合化疗相较于单独化疗并不会提高不良反应发生率(OR=1.32,95%CI:1.13~1.55,P=0.23),差异无统计学意义(P>0.05)。结论卡瑞利珠联合化疗方案相较于单独化疗方案而言,能更有效的提高非小细胞肺癌患者总体缓解率和CD4^(+)/CD8^(+)比值,降低血清肿瘤标志物绝对值,不会升高不良反应发生率,安全性较好。

Objective To discuss the difference in efficacy and safety of immune checkpoint inhibitor camrelizumab alone and combined chemotherapy in the treatment of non-small cell lung cancer.Aggregate analysis of multiple clinical trial data was conducted to obtain more accurate efficacy and safety evaluation,and bring effective information and medication guidance to clinical patients.Methods By searching PubMed,Embase,Cochrane Library,CBM database,CNKI,VIP Chinese database and Wanfang database,we collected the required randomized controlled trials or non-randomized controlled trials published until November 30,2023.After data extraction,Revman5.4 software was applied for data analysis.According to the different treatment plan,the study subjects were divided into camrelizumab combined chemotherapy group and chemotherapy group alone for research discussion.Results A total of 19 articles were included,with a total of 1 545 patients.Meta results showed:compared with chemotherapy alone,camrelizumab combined with chemotherapy in the treatment of nonsmall lung cancer was more effective in improving the overall response rate(OR = 2.50,95%CI:2.02~3.08,P <0.000 01),increased the CD4^(+)/CD8^(+) ratio(MD = 0.26,95%CI:0.19~0.33,P < 0.000 01) and effectively reduced the serum tumor marker CA125(MD =-10.65,95%CI:-14.34~-6.96,P < 0.000 01) and CEA(MD = 5.56,95%CI:-7.64~-3.47,P < 0.000 01),CY211(MD =-2.17,95%CI:-3.22~1.13,P = 0.000 01).Different adverse reactions showed different cluster analysis results.Among them,camrelizumab combined chemotherapy increased anemia(OR = 1.95,95%CI:1.09~3.51,P = 0.03),hypothyroidism(OR = 5.61,95%CI:1.82~17.25,P = 0.003) and capillary hyperplasia(OR = 2.86,95%CI:1.19~6.88,P = 0.02) compared with chemotherapy alone,P values were all < 0.05,and the difference was statistically significant.However,rash( OR = 1.34,95%CI:0.82~2.16,P = 0.24),myelosuppression(OR = 1.06,95%CI:0.56~2.02,P = 0.86),leukopenia(OR =0.78,95%CI:0.40 ~1.52,P = 0.47),alopecia( OR = 1.29,95%CI:0.57 ~2.92,P = 0.54),neurological abnormalities( OR = 1.17,95%CI:0.39 ~3.56,P = 0.78),digestive tract abnormalities( OR = 1.10,95%CI:0.79~1.53,P = 0.57),liver function abnormalities(OR = 1.54,95%CI:0.92~2.59,P = 0.10),nausea and vomiting(OR = 1.16,95%CI:0.58~2.31,P = 0.67),coughing up blood(OR = 0.87,95%CI:0.30~2.49,P = 0.79),fever(OR = 1.22,95%CI:0.65~2.30,P = 0.54) and others(OR = 1.32,95%CI:0.76~2.31,P =0.32) had no significant change in the incidence of symptoms,and all P values were greater than 0.05,the difference was not statistically significant.Taking into account the incidence of all kinds of adverse reactions mentioned above,in general,camrelizumab combined chemotherapy did not increase the incidence of adverse reactions compared with chemotherapy alone(OR = 1.32,95%CI:1.13~1.55,P = 0.23),with a P value greater than 0.05,and the difference was not statistically significant.Conclusion Compared with chemotherapy alone,camrelizumab combined chemotherapy can more effectively improve the overall response rate and CD4^(+)/CD8^(+) ratio in patients with non-small cell lung cancer,reduce the absolute value of serum tumor markers,and does not increase the incidence of adverse reactions,with good safety.