论文部分内容阅读
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,P<0.05。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,P<0.05。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。
Purpose The NCCN guidelines recommend a standard regimen of anti-VEGF or anti-EGFR as first-line therapy for RAS wild-type metastatic colorectal cancer (mCRC), but a rare systematic review of the differential prognosis between anti-VEGF and anti-EGFR in metastatic colorectal cancer reference. This study intends to analyze the impact of anti-VEGF and anti-EGFR targeted drug combination chemotherapy on metastatic colorectal cancer efficacy through systematic review. METHODS: Cochrane, Pubmed, Web of science, Embase, ASCO, ESMO, Clinical Trials and China Biomedical Literature Database were searched by computer. Randomized controlled trial (RCT) of anti-VEGF combined with anti-VEGF and anti-EGFR combined with chemotherapy for head-to-head mCRC was performed. Meta-analysis was performed using Stata 12.0 and Revman 5.3 according to the Cochrane systematic evaluation manual 5.3 Quality Evaluation Criteria. Results A total of 3 randomized controlled trials were enrolled in a total of 2 014 cases. Meta-analysis showed that patients with mCRC treated with either anti-EGFR or anti-VEGF first-line therapy had no significant difference in KRAS wild type (HR = 1.03, 95% CI 0.93-1.13) or wild type RAS (HR 0.92, 95% 1.18) had no significant difference in PFS (P <0.05). Overall survival (OS) for first-line anti-EGFR combination chemotherapy was significantly higher in patients with KRAS wild-type (HR = 0.82; 95% CI 0.72-0.93) and RAS wild-type (HR 0.79; 95% CI 0.67-0.93 ) Were superior to anti-VEGF combined chemotherapy, P <0.05. The objective response rate (ORR) was significantly improved in patients with mCRC and KRAS wild type, with RR = 0.84 and 95% CI 0.76 to 0.94. This advantage was more pronounced for all RAS wild-type patients, RR = 0.80, 95% CI 0.68 ~ 0.93. Patients with left-sided colorectal cancer had survival-benefit PFS (HR = 0.64; 95% CI 0.45 to 0.91) and OS (HR 0.53, 95% CI 6) in patients with right-sided colon cancer regardless of anti-EGFR or anti- CI 0.36 ~ 0.76). Conclusion The first-line treatment of patients with mCRC with KRAS or wild-type RAS may be the best alternative to anti-VEGF therapy as an initial treatment for advanced mCRC. With regard to the location of the tumor, left-colon tumors have a better survival advantage than patients with right-sided colon tumors regardless of the targeted drug therapy.