抗血管生成药物阿柏西普治疗转移性结直肠癌的快速卫生技术评估

Rapid health technology evaluation of anti-angiogenic drug aflibercept in the treatment of metastatic colorectal cancer

目的:采用快速卫生技术评估工具,评价抗血管生成药物阿柏西普治疗转移性结直肠癌(metastatic colorectal cancer,mCRC)的有效性、安全性和经济性,以期为临床医生和专家提供循证依据。方法:经计算机检索中英文数据库包括PubMed,Web of Science以及中国知网和万方等,经2位评价者按照纳入和排除标准独立筛选提取文献资料,进行质量评价,对研究结果采用描述性分析进行分类总结。结果:从488篇文献中经过逐层筛选后最终纳入研究有6个,其中3篇为Meta分析,3篇为药物经济学研究。与单纯的FOLFOX4/FOLFIRI标准化疗方案相比,阿柏西普联合FOLFOX4/FOLFIRI治疗mCRC可显著提高患者的3年生存率(OR:0.52,95%CI:0.35~0.79,P=0.002)和3年无进展生存率(OR:0.63,95%CI:0.45~0.89,P=0.008),差异具有统计学意义。安全性评价方面,阿柏西普联合FOLFOX4/FOLFIRI方案总不良反应发生率低于对照组(FOLFOX4/FOLFIRI)(OR:0.58,95%CI:0.40~0.84,P=0.004),恶心呕吐、白细胞减少、食欲减退及腹泻发生率均显著低于对照组,二者比较具有统计学差异。与对照组相比,阿柏西普所致的胃肠道穿孔与高血压总发生率和高危级均显著增加,具有统计学差异。药物经济学方面结果显示,与单纯的FOLFIRI化疗方案相比,阿柏西普联合化疗方案可以延长mCRC患者的质量生命调整年,阿柏西普联合FOLFIRI化疗方案较雷莫卢单抗联合化疗成本效益比更优,具有经济学优势。结论:阿柏西普联合FOLFOX4/FOLFIRI化疗方案治疗mCRC的有效性和安全性均较好,在日本和美国皆具有较好的经济学优势,是治疗mCRC患者的有效策略。

Objective:To evaluate the effectiveness,safety and economics of the anti-angiogenic drug aflibercept in the treatment of metastatic colorectal cancer(mCRC)using rapid health technology assessment(HTA)thus to provide a reference evidence basis for clinicians and experts.Methods:Chinese and English databases including PubMed,Web of Science,CNKI and Wanfang were searched.Two reviewers independently selected and extracted literatures according to inclusion and exclusion criteria,conducted quality evaluation,and used descriptive analysis to classify and summarize the research results.Results:After gradual screening of 488 literatures,six studies were finally included for the analysis,of which three were Meta-analysis and three were pharmacoeconomic research.Compared with standard FOLFOX4/FOLFIRI chemotherapy,aflibercept combined with FOLFOX4/FOLFIRI treatment significantly improved the 3-year survival rate of mCRC patients(OR:0.52,95%CI:0.35 to 0.79,P=0.002)and 3-year progression-free survival rate(OR:0.63,95%CI:0.45 to 0.89,P=0.008).The difference was statistically significant.In terms of safety,the total incidence of adverse reactions of aflibercept combined with FOLFOX4/FOLFIRI was lower than that of the control group(FOLFOX4/FOLFIRI)(OR:0.58,95%CI:0.40 to 0.84,P=0.004).The incidences of nausea and vomiting,leukopenia,loss of appetite and diarrhea were statistically significantly lower than those of the control group.Pharmacoeconomic analysis results showed that compared with FOLFIRI chemotherapy,aflibercept combined with chemotherapy could prolong the quality life adjustment years of patients with mCRC,and aflibercept combined with FOLFIRI chemotherapy was more cost-effective than rameximab combined with chemotherapy and there were more obvious economic advantages.Conclusion:Aflibercept combined with FOLFOX4/FOLFIRI chemotherapy is effective and safe in the treatment of mCRC.It has good economic advantages in Japan and the United States and is an effective strategy for the treatment of mCRC patients.