Predictive and prognostic value of KRAS mutations in metastatic colorectal cancer patients treated with cetuximab: A meta-analysis of 22 studies
Predictive and prognostic value of KRAS mutations in metastatic colorectal cancer patients treated with cetuximab: A meta-analysis of 22 studies
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DOI：
10.1016/j.ejca.2010.05.022
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发表时间：
2010-10-01
影响因子：
8.4
通讯作者：
Chen, Qing
中科院分区：
文献类型：
--
作者：
Qiu, Li-Xin;Mao, Chen;Chen, Qing
已发表的有关 KRAS 突变对西妥昔单抗治疗的转移性结直肠癌 (mCRC) 的预测和预后价值的数据似乎尚无定论。为了对这种关系进行更精确的估计，进行了荟萃分析。对 PubMed、EMBase、BIOSIS 和 SCOPUS 进行了系统的计算机化检索。总共确定了 22 项研究。根据研究间异质性使用随机效应模型或固定效应模型。最终荟萃分析共纳入 2188 名 mCRC 患者。 KRAS突变率为38%（829/2188）。突变型 KRAS 患者的总体缓解率 (ORR) 为 14% (119/829)，而野生型 KRAS 患者的 ORR 为 39% (529/1359)。当突变型 KRAS 患者与野生型 KRAS 患者进行比较时，ORR 的总体汇总相对比 (RR) 为 0.24（95% 置信区间 (CI)：0.16-0.38；P < 0.01）。与野生型 KRAS 患者相比，突变型 KRAS 患者的中位 PFS 显着缩短（3.0 个月与 5.8 个月；HR = 1.94；95% CI：1.62-2.33；P < 0.01）。同样，与野生型 KRAS 患者相比，突变型 KRAS 患者的中位 OS 显着缩短（6.9 个月与 13.5 个月；HR = 2.17；95% CI：1.72-2.74；P < 0.01）。荟萃分析强烈表明，KRAS 突变代表了接受西妥昔单抗治疗的 mCRC 患者的肿瘤反应和生存的不良预测和预后生物标志物。携带突变型 KRAS 的肿瘤患者在接受西妥昔单抗治疗时更有可能出现更差的反应、PFS 和 OS。 (C) 2010 Elsevier Ltd. 保留所有权利。
The published data on the predictive and prognostic value of KRAS mutations in metastatic colorectal cancer (mCRC) treated with cetuximab seemed inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Systematic computerised searches of the PubMed, EMBase, BIOSIS, and SCOPUS were performed. A total of 22 studies were identified. Random-effects model or fix-effects model was used according to between-study heterogeneity. A total of 2188 mCRC patients were included in the final meta-analysis. The rate of KRAS mutations was 38% (829/2188). The overall response rate (ORR) of mutant KRAS patients was 14% (119/829), whereas the ORR of wild-type KRAS patients was 39% (529/1359). The overall pooled relative ratio (RR) for ORR was 0.24 (95% confidence intervals (CI): 0.16-0.38; P < 0.01) when mutant KRAS patients were compared with wild-type KRAS patients. Median PFS was significantly shorter in mutant KRAS patients compared with that in wild-type KRAS patients (3.0 versus 5.8 months; HR = 1.94; 95% CI: 1.62-2.33; P < 0.01). Similarly, median OS was significantly shorter in mutant KRAS patients compared with that in wild-type KRAS patients (6.9 versus 13.5 months; HR = 2.17; 95% CI: 1.72-2.74; P < 0.01). The meta-analysis strongly suggests that KRAS mutations represent adverse predictive and prognostic biomarkers for tumour response and survival in mCRC patients treated with cetuximab. Patients with tumours that harbour mutant-type KRAS are more likely to have a worse response, PFS, and OS when treated with cetuximab. (C) 2010 Elsevier Ltd. All rights reserved.