Department of Medical Oncology, Cancer Hospital, Fudan University, Shanghai, China.
Eur J Cancer. 2010 Oct;46(15):2781-7. doi: 10.1016/j.ejca.2010.05.022. Epub 2010 Jun 25.
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.
在接受西妥昔单抗治疗的转移性结直肠癌（mCRC）患者中，KRAS 突变的预测和预后价值的已发表数据似乎没有定论。为了更准确地评估这种关系，进行了荟萃分析。系统地检索了 PubMed、EMBase、BIOSIS 和 SCOPUS 数据库。共确定了 22 项研究。根据研究间的异质性，使用随机效应模型或固定效应模型。最终的荟萃分析共纳入了 2188 例 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 患者相比时，ORR 的总体合并相对比值（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 患者的中位无进展生存期（PFS）明显更短（3.0 个月对 5.8 个月；HR=1.94；95%CI：1.62-2.33；P<0.01）。同样，突变型 KRAS 患者的中位总生存期（OS）也明显短于野生型 KRAS 患者（6.9 个月对 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 突变是接受西妥昔单抗治疗的 mCRC 患者肿瘤反应和生存的不良预测和预后生物标志物。携带 KRAS 突变型肿瘤的患者在接受西妥昔单抗治疗时更有可能出现较差的反应、PFS 和 OS。
