KRAS突变对抗EGFR单抗治疗转移性结直肠癌影响的Meta分析

Effect of KRAS mutation in the metastatic colorectal carcinoma patients treated with chemotherapy alone or plus anti-EGFR monoclonal antibodies:a Meta analysis

目的评价化疗或联合抗EGFR单抗治疗转移性结直肠癌的临床疗效与KRAS基因突变的关系。方法用"colorectal carcinoma"、"cetuximab"、"Panitumumab"系统检索PubMed、EMBASE、Ovid、CENTRAL(2000年1月-2011年11月)中关于KRAS突变对化疗或联合抗EGFR单抗(包括Cetuximab和Panitumumab)治疗转移性结直肠癌疗效的影响。结果包括无进展期(progressionfree survival,PFS)和总生存期(overall survival,OS)及其相应HR,依据Cochrane Handbook 5.0.2对符合标准的RCT进行Meta分析。结果 PFS的HR在KRAS野生型患者和突变型患者分别为-0.22(95%CI:-0.37^-0.07,P=0.005)和1.07(95%CI:0.88~1.30,P=0.48),OS的HR在KRAS野生型和突变型则为0.83(95%CI:0.82~0.85,P<0.00001)、1.04(95%CI:0.95~1.15,P=0.40)。抗EGFR治疗均未见明显延长KRAS突变型mCRC患者的PFS和OS。结论 KRAS状态是预测mCRC患者抗EGFR治疗疗效的有效生物学标志之一。

Objective To investigate the relationship between effect of chemotherapy alone or plus anti-EGFR monoclonal antibodies in treatment of metastatic colorectal carcinoma （mCRC） patients and KRAS mutation.Methods Comprehensive and systematic searches of the PubMed,EMBASE,Ovid and the Cochrane Central Register of Controlled Trials （CENTRAL） from Jan.2000 to Nov.2011 were performed by MeSH terms for colorectal carcinoma and randomized controlled trials,plus text-words for anti-EGFR antibodies.The outcomes included progression-free survival （PFS） and overalll survival （OS）.Random effects model or x-effects model was used to evaluate hazard ratio （HR） according to heterogeneity among studies.Results Six studies （6 100 patients） were enrolled and KRAS status was reported in 4 745 cases.The HR of PFS for KRAS wild patients assigned to anti-EGFR antibodies was-0.22 （95％ CI：-0.37 ～-0.07,P =0.005） and that for mutant cases was 1.07 （95％ CI：0.88 ～ 1.30,P =0.48）.Similarly,the HR of OS was significantly different in mutant Kras patients 1.04 （95％ CI：0.95 ～ 1.15,P =0.40） compared with wild-type Kras patients 0.83 （95％ CI：0.82 ～ 0.85,P ＜ 0.00001）.Conclusion KRAS status is an significantly prognostic factor in patients with mCRC treated with anti-EGFR antibodies.