Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS study
Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS study
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DOI：
10.1093/annonc/mdq632
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发表时间：
2011-07-01
影响因子：
50.5
通讯作者：
Koralewski, P.
中科院分区：
文献类型：
--
作者：
Bokemeyer, C.;Bondarenko, I.;Koralewski, P.
患者和方法：通过使用从染色组织切片中提取的额外DNA样本扩展生物标志物分析。使用PCR技术确定新样本（以及BRAF现有样本）的KRAS和BRAF肿瘤突变状态。根据突变状态重新评估临床结局。结果：在315例KRAS可评估患者样本（93%）中，179例肿瘤（57%）为KRAS野生型。309例KRAS/BRAF可评价肿瘤中有11例（4%）（均为KRAS野生型）携带BRAF突变。在KRAS野生型肿瘤患者中，西妥昔单抗联合FOLFOX-4治疗显著改善了无进展生存期（风险比0.567，P = 0.0064）和缓解（优势比2.551，P = 0.0027）。结论：这些结果证实了西妥昔单抗联合FOLFOX-4一线治疗KRAS野生型mCRC患者的疗效，并证实KRAS突变状态是一种有效的预测生物标志物。BRAF突变的肿瘤数量较少，无法得出关于该生物标志物的预测或预后效用的明确结论。
Patients and methods: The biomarker analysis was extended through the use of additional DNA samples extracted from stained tissue sections. KRAS and BRAF tumor mutation status was determined for new (and for BRAF, existing) samples using a PCR technique. Clinical outcome was reassessed according to mutation status. Overall survival data are presented.Results: Of 315 KRAS evaluable patient samples (93%), 179 tumors (57%) were KRAS wild type. Eleven of 309 (4%) KRAS/BRAF evaluable tumors (all KRAS wild type) carried BRAF mutations. The addition of cetuximab to FOLFOX-4 significantly improved progression-free survival (hazard ratio 0.567, P = 0.0064) and response (odds ratio 2.551, P = 0.0027) in patients with KRAS wild-type tumors. A favorable effect on survival was also observed.Conclusions: These results confirm the efficacy of cetuximab plus FOLFOX-4 in the first-line treatment of patients with KRAS wild-type mCRC and confirm KRAS mutation status as an effective predictive biomarker. The small number of tumors with BRAF mutations precluded the drawing of definitive conclusions concerning the predictive or prognostic utility of this biomarker.