K-ras基因突变状态与西妥昔单抗/帕尼单抗治疗转移性结直肠肠癌疗效的系统评价

Association between K-ras Mutation and Response to Cetuximab/Panitumumab in Patients with Metastatic Colorectal Cancer

目的评价K-ras基因突变状态与西妥昔单抗／帕尼单抗治疗mCRC疗效间的关系。方法检索Pubmed、CENTRAL（theCochraneCentralRegisterofControlledtrials）、EMBASE、中国期刊全文数据库（CNKI）、美国临床肿瘤学会（ASCO）、欧洲肿瘤协会（EMSO）官方网等，公开发表的K-ras基因突变状态与西妥昔单抗／帕尼单抗治疗mCRC疗效间关系的研究（包括前瞻性和回顾性）。应用Stata11．0统计软件分析K．ras基因突变状态与西妥昔单抗／帕尼单抗治疗mCRC疗效间的关系。结果共12项研究1622例受试者纳入分析，合并分析显示：mCRC患者中K-ras基因突变率为P=39％（95％CI：37％-44％）；K-ras野生型和突变型患者西妥昔单抗／帕尼单抗治疗的客观有效率（CR＋PR）分别为P=18％（95％CI：15％-26％）和P=9％（95％CI：2％～15％）；与K-ras突变型相比，K—ras野生型患者西妥昔单抗／帕尼单抗治疗的客观有效率优势比OR（oddsratio）=5．10（95％CI：2．84～9．14）。结论mCRC中约有40％的患者存在K-ras基因突变，存在K．ras基因突变的患者对抗EGFR治疗（西妥昔单抗肿自尼单抗）反应较差。

OBJECTIVE To evaluate relationship between the K-ras gene mutation status and response to cetuximab/ panitumumab for mCRC. METHODS By searching PubMed, CENTRAL, EMBSE, CNKI, ASCO and ESMO databases, the open published studies about the relationship between the K-ras gene mutation status and response to cetuximab/panitumumab for metastatic colorectal cancer were searched. The pooled ORR for metastatic colorectal cancer treated with cetuximab/panitumumab associated with the K-ras gene mutation status was calculated by statistic software Stata 11.0. RESULTS Twelve studies including 1 622 participants were include in this systematic review and Meta-analysis. The aggregated analysis showed the prevalence of K-ras mutation in mCRC was P=-39%（95% CI： 37%-44%）. The ORR （ORR=CR＋PR） in K-ras wild type group and mutation group treated with aiti-EGFR were P=-18%（95% CI： 15%-26%） and P=-9%（95% CI： 2%-15%） respectively. The odds of ORR in K-ras wild type group was much higher than that in K-ras mutation group OR=5.10（95% CI： 2.84-9.14）. CONCLUSION About 40% patients with mCRC have mutated K-ras gene which indicated the poor response to anti-EGFR treatment.