Cetuximab Plus Irinotecan, Fluorouracil, and Leucovorin As First-Line Treatment for Metastatic Colorectal Cancer: Updated Analysis of Overall Survival According to Tumor KRAS and BRAF Mutation Status
Cetuximab Plus Irinotecan, Fluorouracil, and Leucovorin As First-Line Treatment for Metastatic Colorectal Cancer: Updated Analysis of Overall Survival According to Tumor KRAS and BRAF Mutation Status
复制标题
DOI：
10.1200/jco.2010.33.5091
复制
发表时间：
2011-05-20
影响因子：
45.3
通讯作者：
Ciardiello, Fortunato
中科院分区：
文献类型：
--
作者：
Van Cutsem, Eric;Kohne, Claus-Henning;Ciardiello, Fortunato
研究目的：西妥昔单抗联合伊立替康、氟尿嘧啶和亚叶酸（FOLFIRI）作为转移性结直肠癌（mCRC）的一线治疗，可降低KRAS野生型患者疾病进展的风险，增加缓解的机会。一个更新的生存分析，包括额外的患者分析肿瘤突变状态，carried.Patients和MethodsPatients被随机分配到接受FOLFIRI或不西妥昔单抗。从先前用于评估表皮生长因子受体表达的额外载玻片固定的肿瘤样品中提取DNA。根据肿瘤KRAS和BRAF突变状态的临床结果进行了评估，在扩大patient series.ResultsThe的确诊率分析肿瘤KRAS状态的患者从45%增加到89%，与突变检测到37%的肿瘤。在KRAS野生型疾病患者中，西妥昔单抗联合FOLFIRI治疗可显著改善总生存期（中位数，23.5 vs 20.0个月;风险比[HR]，0.796; P = .0093），无进展生存期（中位数，9.9 vs 8.4个月; HR，0.696; P = 0.0012）和反应（率57.3% vs 39.7%;比值比，2.069; P <0.001）与FOLFIRI单独治疗相比。对于所有关键疗效终点，均观察到KRAS状态与治疗效果之间的显著相互作用。KRAS突变状态被证实是西妥昔单抗联合FOLFIRI疗效的有力预测生物标志物。BRAF肿瘤突变是预后不良的一个强有力的指标。ConclusionThe addition of cetuximab to FOLFIRI as first line therapy improves survival in patients with KRAS wild-type mCRC. BRAF肿瘤突变是预后不良的指标。
PurposeThe addition of cetuximab to irinotecan, fluorouracil, and leucovorin (FOLFIRI) as first-line treatment for metastatic colorectal cancer (mCRC) was shown to reduce the risk of disease progression and increase the chance of response in patients with KRAS wild-type disease. An updated survival analysis, including additional patients analyzed for tumor mutation status, was undertaken.Patients and MethodsPatients were randomly assigned to receive FOLFIRI with or without cetuximab. DNA was extracted from additional slide-mounted tumor samples previously used to assess epidermal growth factor receptor expression. Clinical outcome according to the tumor mutation status of KRAS and BRAF was assessed in the expanded patient series.ResultsThe ascertainment rate of patients analyzed for tumor KRAS status was increased from 45% to 89%, with mutations detected in 37% of tumors. The addition of cetuximab to FOLFIRI in patients with KRAS wild-type disease resulted in significant improvements in overall survival (median, 23.5 v 20.0 months; hazard ratio [HR], 0.796; P = .0093), progression-free survival (median, 9.9 v 8.4 months; HR, 0.696; P = .0012), and response (rate 57.3% v 39.7%; odds ratio, 2.069; P < .001) compared with FOLFIRI alone. Significant interactions between KRAS status and treatment effect were noted for all key efficacy end points. KRAS mutation status was confirmed as a powerful predictive biomarker for the efficacy of cetuximab plus FOLFIRI. BRAF tumor mutation was a strong indicator of poor prognosis.ConclusionThe addition of cetuximab to FOLFIRI as first-line therapy improves survival in patients with KRAS wild-type mCRC. BRAF tumor mutation is an indicator of poor prognosis.