Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: Pooled analysis of the CRYSTAL and OPUS randomised clinical trials
Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: Pooled analysis of the CRYSTAL and OPUS randomised clinical trials
复制标题
DOI：
10.1016/j.ejca.2012.02.057
复制
发表时间：
2012-07-01
影响因子：
8.4
通讯作者：
Koehne, Claus-Henning
中科院分区：
文献类型：
--
作者：
Bokemeyer, Carsten;Van Cutsem, Eric;Koehne, Claus-Henning
背景资料：CRYSTAL和OPUS随机临床试验表明，与单用化疗相比，在KRAS野生型转移性结直肠癌（mCRC）患者的一线化疗中添加西妥昔单抗可显著改善治疗结局。本汇总分析的目的是使用延长的生存期数据并在这些研究中提高KRAS和BRAF肿瘤突变状态的确定率后，进一步研究KRAS野生型肿瘤患者的这些结果。分析来自每项研究的汇总个体患者数据的总生存期（OS），KRAS和BRAF突变状态可评价患者的无进展生存期（PFS）和最佳总缓解率（ORR）。结果：在845例KRAS野生型肿瘤患者中，西妥昔单抗联合化疗可显著改善OS（风险比[HR] 0.81; p = 0.0062）、PFS（HR 0.66; p < 0.001）和ORR（优势比2.16; p < 0.0001）。在70/800个可评价肿瘤中检测到BRAF突变。在这些患者中，治疗组之间的结局无显著差异。与BRAF野生型tumors.Conclusion：从CRYSTAL和OPUS研究的汇总数据分析证实了从KRAS野生型mCRC患者的一线化疗中加入西妥昔单抗的所有疗效终点获得的益处的一致性。BRAF突变似乎不是这种情况下的预测性生物标志物，但却是预后不良的标志物。(C)2012爱思唯尔有限公司保留所有权利。
Background: The CRYSTAL and OPUS randomised clinical trials demonstrated that adding cetuximab to first-line chemotherapy in patients with KRAS wild-type metastatic colorectal cancer (mCRC) significantly improved treatment outcome compared with chemotherapy alone. The objective of this pooled analysis was to further investigate these findings in patients with KRAS wild-type tumours using extended survival data and following an enhancement in the ascertainment rate of KRAS and BRAF tumour mutation status from these studies.Methods: Pooled individual patient data from each study were analysed for overall survival (OS), progression-free survival (PFS) and best overall response rate (ORR) in patients evaluable for KRAS and BRAF mutation status. Treatment arms were compared according to mutation status using log-rank and Cochran-Mantel-Haenszel tests.Results: In 845 patients with KRAS wild-type tumours adding cetuximab to chemotherapy led to a significant improvement in OS (hazard ratio [HR] 0.81; p = 0.0062), PFS (HR 0.66; p < 0.001) and ORR (odds ratio 2.16; p < 0.0001). BRAF mutations were detected in 70/800 evaluable tumours. No significant differences were found in outcome between the treatment groups in these patients. Prognosis was worse in each treatment arm for patients with BRAF tumour mutations compared with those with BRAF wild-type tumours.Conclusion: Analysis of pooled data from the CRYSTAL and OPUS studies confirms the consistency of the benefit obtained across all efficacy end-points from adding cetuximab to first-line chemotherapy in patients with KRAS wild-type mCRC. BRAF mutation does not appear to be a predictive biomarker in this setting, but is a marker of poor prognosis. (C) 2012 Elsevier Ltd. All rights reserved.