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

关键词:  转移性结直肠癌  K-ras基因  西妥昔单抗/帕尼单抗  Meta分析

Key words:  metastatic colorectal cancer  K-ras gene  cetuximab/panitumumab  Meta-analysis

摘要:

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(the Cochrane Central Register of Controlledtrials)、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Stata 11.0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1 622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(odds ratio)=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/帕尼单抗)反应较差。

Abstract:

ABSTRACT: 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.