曲氟尿苷替匹嘧啶联合贝伐珠单抗治疗难治性转移性结直肠癌的疗效与安全性的meta分析

Efficacy and safety of trifluridine-tipiracil combined with bevacizumab for refractory metastastic colorectal cancer:a meta-analysis

目的系统分析曲氟尿苷替匹嘧啶(trifluridine-tipiracil/TAS-102,T)联合贝伐珠单抗(bevacizumab,B)相较于TAS-102单药在既往标准治疗失败或不耐受的难治性转移性结直肠癌(metastastic colorectal cancer,m CRC)应用中的有效性和安全性。方法在PubMed、Embase和Cochrane Library中进行文献检索,检索时限为自建库至2020年7月,并对纳入的文献进行meta分析,并采用相对危险度(relative risk,RR)及风险比(hazard ratio,HR)作为合并效应量。结果共纳入4篇文献,包括1项随机对照试验(randomized controlled trial,RCT)和3项回顾性研究,共338例患者(T+B组:163例,T组:175例)。T+B组疾病控制率(RR=1.71,95%CI:1.11~2.61,P=0.01)、无进展生存期(HR=0.59,95%CI:0.44~0.78,P=0.0002)、总生存期(HR=0.58,95%CI:0.43~0.79,P=0.0006)均高于T组。在任何级别的不良事件中,T+B组中性粒细胞减少症、血小板减少症、高血压、蛋白尿的发生率均高于T组(P<0.05);而两组之间的贫血、恶心、腹泻、呕吐、粒细胞减少性发热、疲乏等症状的差异均无统计学意义(P>0.05);T+B组中3级以上的中性粒细胞减少症与贫血的发生率高于T组(P<0.05)。结论对于难治性m CRC患者,TAS-102联合贝伐珠单抗治疗后的疾病控制率、无进展生存期及总生存期均优于TAS-102单药治疗,但中性粒细胞减少症、血小板减少症、贫血(逸3级)、高血压、蛋白尿发生率较高。

Objective To systematically analyze the efficacy and safety of trifluridine--tipiracil/TAS-102 combined with bevacizumab(B)compared with TAS-102 alone in metastastic colorectal cancer(mCRC)with failure or intolerance to previous standard therapy.Methods We conducted literature search in PubMed,Embase,and Cochrane Library from the self-built database to July 2020.Meta-analysis was performed on the included literatures,and relative risk(RR)and hazard ratio(HR)were used as the combined effect size.Results A total of 338 patients were identified from 4 literatures,including 1 randomized controlled trial(RCT)and 3 retrospective studies.There were statistically significant differences between the TAS-102 plus bevacizumab(T-B group)and TAS-102 monotherapy(T group)in disease control rate(DCR)(RR=1.71,95%CI:1.11-2.61,P=0.01),progression-free survival(PFS)(HR=0.59,95%CI:0.44-0.78,P=0.0002)and overall survival(OS)(HR=0.58,95%CI:0.43-0.79,P=0.0006).Among the treatment-related adverse events(AEs)of any grade,the incidence rates of neutropenia,thrombocytopenia,hypertension and proteinuria were higher in T-B group than T group(P<0.05).However,There was no significant difference in anemia,nausea,diarrhea,vomiting,granulocytopenic fever,fatigue and other symptoms between the two groups(P>0.05).And the incidence rates of grade≥3 neutropenia and anemia was significantly higher in the T-B group than in T group(P<0.05).Conclusion Treatment strategy of TAS-102 combined with bevacizumab was associated with significant better PFS rate,OS and DCR compared with TAS-102 monotherapy in patients with refractory mCRC.However,the incidence rate of neutropenia,thrombocytopenia,anemia(grade≥3),hypertension,and proteinuria were higher.