KRAS p.G13D Mutation and Codon 12 Mutations Are Not Created Equal in Predicting Clinical Outcomes of Cetuximab in Metastatic Colorectal Cancer A Systematic Review and Meta-Analysis
KRAS p.G13D Mutation and Codon 12 Mutations Are Not Created Equal in Predicting Clinical Outcomes of Cetuximab in Metastatic Colorectal Cancer A Systematic Review and Meta-Analysis
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DOI：
10.1002/cncr.27804
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发表时间：
2013-02-15
期刊：
影响因子：
6.2
通讯作者：
Tang, Jin-Ling
中科院分区：
文献类型：
--
作者：
Mao, Chen;Huang, Ya-Fang;Tang, Jin-Ling
背景：作者进行了一项系统的综述和荟萃分析，以检验具有v-ki-ras2 Kirsten鼠肉瘤病毒癌基因同源(KRAS)p.G13D突变(KRAS基因第13位氨基酸从甘氨酸替换为天冬氨酸)并接受西妥昔单抗治疗的转移性结直肠癌患者是否比具有KRAS密码子12突变的转移性结直肠癌患者有更好的临床结果。方法：应用计算机检索MEDLINE、EMBASE、中国生物医学数据库、万方数字期刊，检索词为MEDLINE、EMBASE、《万方数字期刊》。主要临床结果包括客观有效率(ORR)、无进展生存期(PFS)和总生存期(OS)。根据研究之间的异质性，使用固定效应或随机效应模型估计合并的相对危险度(RR)或危险比(HR)。结果：10项研究被认为是合格的，其中包括1487例多发性结直肠癌患者。与具有KRAS密码子12突变的肿瘤患者相比，具有KRAS p.G13D突变的肿瘤患者的ORR(10项研究；RR，1.642；95%可信区间[CI]，1.131-2.384)、PFS(1项研究；HR，0.54；95%CI，0.36-0.81)和OS(1项研究；HR，0.52；95%CI，0.33-0.80)显著增加。与KRAS野生型肿瘤患者相比，p.G13D突变患者的ORR(9个研究；RR，0.540；95%CI，0.381~0.765)显著降低，PFS(1个研究；HR，0.99；95%CI，0.68~1.45)和OS(1个研究；HR，1.01；95%CI，0.66~1.54)无明显缩短。结论：具有KRAS p.G13D突变的mCRC患者似乎比具有KRAS密码子12突变的肿瘤患者从西妥昔单抗中获益更多。然而，由于目前荟萃分析的样本量有限，对这些结果的解释应谨慎。癌症2013年。(C)2012年美国癌症协会。
BACKGROUND: The authors conducted a systematic review and meta-analysis to examine whether patients who had metastatic colorectal cancer (mCRC) with the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) p.G13D mutation (an amino acid substitution at position 13 in KRAS from a glycine to an aspartic acid) and received cetuximab treatment had better clinical outcomes than patients who had mCRC tumors with KRAS codon 12 mutations. METHODS: Relevant studies were identified by a search of MEDLINE, EMBASE, the Chinese Biomedical Database, and Wan Fang Digital Journals from inception to October 2011. The primary clinical outcomes included the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The pooled relative risk (RR) or hazard ratio (HR) was estimated by using fixed-effects or random-effects models according to heterogeneity between studies. RESULTS: Ten studies were considered eligible that included 1487 patients with mCRC. Patients who had tumors with the KRAS p.G13D mutation had a significantly higher ORR (10 studies; RR, 1.642; 95% confidence interval [CI], 1.131-2.384), longer PFS (1 study; HR, 0.54; 95% CI, 0.36-0.81), and longer OS (1 study; HR, 0.52; 95% CI, 0.33-0.80) than patients who had tumors with KRAS codon 12 mutations. Compared with patients who had KRAS wild-type tumors, patients with the p.G13D mutation had a significantly lower ORR (9 studies; RR, 0.540; 95% CI, 0.381-0.765) and nonsignificantly shorter PFS (1 study; HR, 0.99; 95% CI, 0.68-1.45) and OS (1 study; HR, 1.01; 95% CI, 0.66-1.54). CONCLUSIONS: Patients who had mCRC with the KRAS p.G13D mutation appeared to benefit more from cetuximab than patients who had tumors with KRAS codon 12 mutations. However, because of the limited sample sizes in the current meta-analysis, these results should be interpreted with caution. Cancer 2013. (c) 2012 American Cancer Society.