【摘要】 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。更多还原

【Abstract】 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.更多还原