作者：高雅媚1,2，王斌2,王亚梅1,2，贾漪涛2

单位：1.河北医科大学研究生学院，河北 石家庄 050017；2.河北省人民医院 肿瘤三科，河北 石家庄 050051

Authors: Gao Yamei1,2，Wang Bin2，Wang Yamei1,2，Jia Yitao2

Unit: 1. Graduate school of Hebei Medical University, Shijiazhuang 050017, Hebei,China；2.Third Department of Oncology, Hebei General Hospital, Shijiazhuang 050051, Hebei,China

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(≥3级)、高血压、蛋白尿发生率较高。

关键词：结直肠癌；曲氟尿苷替匹嘧啶；贝伐珠单抗；meta分析

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.

Key Words: Colorectal neoplasms；Trifluridine-tipiracil；Bevacizumab；Meta-analysis