贝伐单抗联合化疗一线治疗转移性结直肠癌的Meta分析
Bevacizumab Combined with Chemotherapy as First-line Therapy for Metastatic Colorectal Cancer: A Meta-analysis
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摘要: 目的 评价贝伐单抗（bevacizumab,BEV)联合化疗一线治疗转移性结直肠癌（metastatic colorectal cancer, mCRC）的有效性和安全性。方法 通过The Cochrane Library、PubMed、EMBASE 和中国生物医学文献数据库（CBM）、中国期刊全文数据库（CNKI）、维普数据库（VIP）、万方数据库等检索有关BEV联合化疗一线治疗mCRC的随机对照试验（randomized control trial, RCT）；主要研究指标是无进展生存时间（progression free survival, PFS）和总生存时间（overall survival, OS），次要研究指标包括有效率（objective response rate, ORR）和不良反应；采用相对危险度（relative risk, RR）和风险比（hazard ratios, HR）为效应量，各效应量以95%置信区间（95%CI）表示，Stata 11.0统计软件进行Meta分析。结果 共纳入9项RCT，共3 930例mCRC患者，Meta分析结果显示，与单纯化疗相比，贝伐单抗(bevacizumb, BEV)联合化疗可以降低疾病进展风险（HR=0.62, P<0.0001, 95%CI: 0.64~0.74）和疾病死亡风险（HR=0.84, P<0.001,95%CI: 0.73~0.95），提高mCRC 的ORR（RR=0.80, P<0.001,95%CI: 0.60~0.93）。亚组分析显示BEV联合双药方案可降低疾病进展风险（HR=0.68, P<0.001, 95%CI: 0.46~0.89），但并没有降低疾病死亡风险（HR=0.85, P=0.068,95%CI:0.68~1.03）；BEV联合氟尿嘧啶类单药降低疾病进展风险（HR=0.56,P<0.001, 95%CI: 0.47~0.64）和疾病死亡风险（HR=0.83,P<0.001,95%CI:0.68~0.97）。在不良反应方面，B E V 联合化疗没有增加治疗相关死亡率（RR=0.97, P=0.91,95%CI:0.62~1.54）；增加BEV相关不良反应发生率。结论 BEV联合化疗一线治疗能提高mCRC患者PFS、OS和RR。BEV联合不同化疗方案所带来生存获益大小不同。虽然BEV相关不良反应增加，但是可控的。Abstract: Objective To assess the efficacy and safety of bevacizumab(BEV) combined with chemotherapy as a first-line therapy for metastatic colorectal cancer(mCRC). Methods A wide search of randomized clinical trials using BEV combined with chemotherapy as a first-line therapy for mCRC patients was performed in the Cochrane Library，PubMed，EmBase and CBM，CNKI，VIP，WanFang databases. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes were objective response rate (ORR) and toxicity. Relative risk (RR) and hazard ratios (HR) were expressed by 95% confidence intervals (95%CI). The software Stata 11.0 was used for meta-analysis. Results We involved 9 RCT trials, totally 3930 patients. Meta analysis indicated that compared with chemotherapy alone, BEV combined with chemotherapy could decrease the risk of progressive disease（HR=0.62, P<0.0001, 95%CI: 0.64-0.74）and the risk of disease death（HR=0.84, P<0.001, 95%CI: 0.73-0.95）, and could increase the ORR of mCRC patients（RR=0.80, P<0.001, 95%CI: 0.60-0.93）. Subgroup analysis indicated that the combination of BEV and double therapy could decrease the risk of progressive disease（HR=0.68, P<0.001, 95%CI: 0.46-0.89），but no decrease in the risk of disease death(HR=0.85, P=0.068, 95%CI: 0.68-1.03). The combination of BEV and monotherapy could decrease the risk of progressive disease(HR=0.56, P<0.001, 95%CI: 0.47-0.64) and the risk of disease death(HR=0.83, P<0.001, 95%CI: 0.68-0.97). Regarding the toxicity, BEV combined with chemotherapy didn't increase the treatment-related mortality(RR=0.97, P=0.91, 95%CI: 0.62-1.54), but increased the rates of BEV-associated adverse effects. Conclusion BEV combined with chemotherapy as a first-line treatment could increase the PFS,OS and ORR of mCRC patients. The benefit was dissimilar between BEV with monotherapy and BEV with double therapy. Although the BEVassociated adverse effect was increased, they could be controlled.
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