抗EGFR单抗与抗VEGF单抗联合治疗转移性大肠癌的Meta分析

Concurrent use of anti-VEGF and anti-EGFR antibodies in the treatment of metastatic colorectal cancer: A Meta-analysis of randomized controlled trials

目的：以Meta分析方法探讨抗EGFR单抗与抗VEGF单抗联合治疗转移性大肠癌的疗效与安全性。方法：检索Pubmed/MEDLINE，Ovid/EMBASE，Cochrane等数据库及相关组织的会议文章获得随机对照研究的文献，两名研究员独立对文献进行筛选、质量评价和数据提取，采用R 2.15.1统计软件中的“Meta”软件包进行分析。结果：共纳入4篇文献，包含了5个研究、共2 059例患者。与对照组仅用单种单抗治疗相比，试验组使用两种单抗联合治疗转移性大肠癌患者的无进展生存时间更短[RR=1.12，95% CI（1.05~1.19）]；总体生存时间[RR=1.17，95% CI（0.98~1.40）]、总体缓解率[RR=0.97，95% CI（0.89~1.07）] 无明显差别。试验组的3/4级皮肤毒性[RR=12.62，95% CI（1.90~83.84）]、3/4级感染[RR=1.53，95% CI（1.13~2.08）]发生率高于对照组；3/4级胃肠道不良事件[RR=1.48，95% CI（0.79~2.77）]和3/4级静脉血栓[RR=1.18，95% CI（0.84~1.65）]发生率与对照组相当；3/4级高血压[RR=0.61，95% CI（0.42~0.87）]和3/4级神经系统不良事件[RR=0.54，95% CI（0.37~0.80）]的发生率低于对照组。结论：与单种单抗治疗相比，两种单抗联合治疗转移性大肠癌的无进展生存时间更短，总体生存时间和总体缓解率无明显改善，皮肤毒性和感染等常见的不良事件发生率有所上升。

Objective ： To systematically evaluate the efficacy and safety of the concurrent use of anti-VEGF and anti-EGFR antibodies in patients with metastatic colorectal cancer. Methods： PubMed/MEDLINE，Ovid/EMBASE, Cochrane and some other databases together with related meeting abstracts were searched for randomized controlled trials on this topic by two independent researchers. Data were extracted from the included studies and analyzed using Review Manager 5.0.23. Results： A total of 2059 patients in five studies were included in this Meta-analysis. Compared with the control treatment involving an anti-VEGF or anti-EGFR antibody alone, the concurrent use of anti-VEGF and anti-EGFR antibodies decreased the progression-free survival （RR＝1.12, 95% CI： 1.05-1.19） as. Patients in the two treatment groups did not differ significantly in either overall survival （RR＝1.17, 95% CI： 098-1.40） or overall response rate （RR＝097, 95% CI： 0.89-1.07）. There were significant differences between the two groups in grade 3/4 adverse cutaneous events （RR＝12.62, 95% CI： 1.90-83.84）, grade 3/4 infection （RR＝153, 95% CI： 1.13-2.08）, grade 3/4 hypertension （RR＝0.61, 95% CI： 0.42-0.87）, and grade 3/4 adverse events of nervous system （RR＝0.54, 95% CI： 037-0.80） but not in grade 3/4 adverse gastrointestinal events （RR＝1.48, 95% CI： 0.79-2.77） and grade 3/4 venous thrombosis （RR＝1.18, 95% CI： 0.84-1.65）. Conclusion： The concurrent use of anti-VEGF and anti-EGFR antibodies offer no additional benefits for patients with metastatic colorectal cancer as compared with the use of theses antibodies each alone and therefore should not be recommended in clinics.