抗VEGF与抗EGFR靶向药物联合化疗一线治疗转移结直肠癌Meta分析

发布时间：2019-01-21 18:14

【摘要】：目的 NCCN指南推荐抗VEGF或抗EGFR作为伴RAS野生型的转移结直肠癌(metastatic colorectal cancer,mCRC)一线治疗的标准方案,但抗VEGF与抗EGFR在转移结直肠癌预后的差异性罕见系统评价参考。本研究拟通过系统评价分析抗VEGF与抗EGFR靶向药物联合化疗对转移结直肠癌疗效的影响。方法计算机检索Cochrane、Pubmed、Web of science、Embase、ASCO、ESMO、Clinical Trials和中国生物医学文献数据库等,同时追溯参考文献。收集抗VEGF联合化疗对比抗EGFR联合化疗治疗mCRC头对头的随机对照试验(Randomized controlled trial,RCT),根据Cochrane系统评价手册5.3质量评价标准,采用Stata 12.0和Revman 5.3进行Meta分析。结果共纳入3篇临床随机对照试验,共2 014例研究对象。Meta分析结果显示,一线给予抗EGFR或抗VEGF联合化疗的mCRC患者,无论KRAS野生型(HR=1.03,95%CI为0.93~1.13)或RAS野生型(HR=0.92,95%CI为0.71~1.18)的无进展生存期(pogression free survival,PFS)均差异无统计学意义,P0.05。一线给予抗EGFR联合化疗方案的总生存期(overall survival,OS)KRAS野生型(HR=0.82,95%CI为0.72~0.93)和RAS野生型患者(HR=0.79,95%CI为0.67~0.93)均优于抗VEGF联合化疗,P0.05。mCRC伴KRAS野生型患者,接受抗EGFR联合化疗客观缓解率(objective response rate,ORR)显著提高,RR=0.84,95%CI为0.76~0.94;这种优势对于所有的RAS野生型患者更加明显,RR=0.80,95%CI为0.68~0.93。无论使用抗EGFR或抗VEGF联合化疗,左半结直肠癌患者相比右半结肠癌患者有生存获益PFS(HR=0.64,95%CI为0.45~0.91)及OS(HR=0.53,95%CI为0.36~0.76)。结论 mCRC伴KRAS或RAS野生型患者的一线治疗,抗EGFR单克隆抗体可能是替代抗VEGF治疗作为晚期mCRC的初始治疗的最佳治疗方案。而对于肿瘤的位置而言,无论接受何种靶向药物治疗,左半结肠肿瘤相比右半结肠肿瘤的患者都具有更好的生存优势。
[Abstract]:Objective the NCCN guidelines recommend anti VEGF or anti EGFR as the standard regimen for (metastatic colorectal cancer,mCRC with RAS wild-type metastatic colorectal cancer, but the difference between anti VEGF and anti EGFR in the prognosis of metastatic colorectal cancer is a rare systematic evaluation reference. The purpose of this study was to evaluate the effect of combination chemotherapy of anti VEGF and anti EGFR targeting drugs on metastatic colorectal cancer. Methods Cochrane,Pubmed,Web of science,Embase,ASCO,ESMO,Clinical Trials and Chinese biomedical literature database were searched by computer. A randomized controlled trial (Randomized controlled trial,RCT) was conducted to evaluate the effects of anti-VEGF combined chemotherapy and anti-EGFR combination chemotherapy on the head to head of mCRC. According to the quality evaluation criteria of Cochrane system evaluation manual 5.3, Meta analysis was performed with Stata 12.0 and Revman 5.3. Results A total of 2 014 subjects were enrolled in 3 clinical randomized controlled trials. The results of Meta analysis showed that patients with mCRC received first-line chemotherapy with anti-EGFR or anti-VEGF. There was no significant difference in the progression free survival (pogression free survival,PFS) of KRAS wild type (HR=1.03,95%CI = 0.93n1.13) or RAS wild type (HR=0.92,95%CI = 0.71 卤1.18) (P 0.05). The total survival time (overall survival,OS) of KRAS wild-type (HR=0.82,95%CI 0.72) and RAS wild-type (HR=0.79,95%CI 0.670.93) of first-line regimen of anti-EGFR combined chemotherapy were better than that of anti-VEGF combination chemotherapy. The objective remission rate (objective response rate,ORR) of P0.05.mCRC patients with KRAS was significantly higher than that of KRAS patients (RR=0.84,95%CI = 0.760.94). This advantage was more evident in all RAS wild-type patients with RR=0.80,95%CI of 0. 68 / 0. 93. Whether using anti EGFR or anti VEGF combination chemotherapy, patients with left colorectal cancer had survival benefit compared with patients with right colon cancer, PFS (HR=0.64,95%CI = 0. 450.91) and OS (HR=0.53,95%CI = 0. 36V 0. 76). Conclusion mCRC with KRAS or RAS wild-type therapy, anti-EGFR monoclonal antibody may be the best alternative to anti-VEGF therapy as the initial treatment of advanced mCRC. As for the location of tumor, the patients with left colon tumor have better survival advantages than those with right colon tumor regardless of the targeted drug therapy.
【作者单位】：遵义医学院附属肿瘤医院腹部肿瘤科;
【基金】：贵州省科技厅资助项目[黔科合J字(2007)2129]
【分类号】：R735.34

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