Clinical Benefit of High-Sensitivity KRAS Mutation Testing in Metastatic Colorectal Cancer Treated with Anti-EGFR Antibody Therapy
Clinical Benefit of High-Sensitivity KRAS Mutation Testing in Metastatic Colorectal Cancer Treated with Anti-EGFR Antibody Therapy
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DOI：
10.1159/000336792
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发表时间：
2012-01-01
期刊：
影响因子：
3.5
通讯作者：
Takayama, Tetsuji
中科院分区：
文献类型：
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作者：
Kimura, Tetsuo;Okamoto, Koichi;Takayama, Tetsuji
目的：比较高灵敏度KRAS突变检测与直接测序预测抗表皮生长因子受体抗体在转移性结直肠癌（mCRC）患者中的疗效。方法：采用直接测序和高灵敏度的2步PCR限制性片段长度多态性（RFLP）方法分析61例西妥昔单抗治疗的mCRC患者肿瘤的KRAS状态。评估不同突变状态下的治疗效果。结果：直接测序和2步PCR RFLP检测KRAS突变的发生率分别为34.4和52.5% （p = 0.02）。两种方法将患者分为3组[W/W，野生型（n = 29）；W/M，直接测序野生型，2步PCR RFLP检测突变（n = 11）；M/M，两种方法的突变型（n = 21）]。西妥昔单抗在W/M组的有效率（0%）与M/M组相同，显著低于W/W组（41.4%）（p < 0.001）。W/M组的无进展生存期（11.0周）与M/M组（8.0周）相似，明显短于W/W组（18.0周）（p < 0.002）。结论：高灵敏度KRAS突变检测可用于筛选西妥昔单抗的真正应答者。巴塞尔S. Karger股份有限公司版权所有
Objective: We compared high-sensitivity KRAS mutation testing with direct sequencing for predicting the efficacy of antiepidermal growth factor receptor antibodies in patients with metastatic colorectal cancer (mCRC). Methods: We analyzed the KRAS status in 61 tumors from cetuximab-treated mCRC patients by both direct sequencing and a high-sensitivity method: 2-step PCR restriction fragmentation length polymorphism (RFLP). Therapeutic effects in each mutational status were evaluated. Results: The incidences of KRAS mutations determined by direct sequencing and 2-step PCR RFLP were 34.4 and 52.5%, respectively (p = 0.02). Patients were categorized into 3 groups [W/W, wild-type by both methods (n = 29); W/M, wild-type by direct sequencing, detected mutation by 2-step PCR RFLP (n = 11); M/M, mutant-type by both methods (n = 21)]. The response rate for cetuximab in the W/M group (0%) was the same as that in the M/M group, and was significantly lower than in the W/W group (41.4%) (p < 0.001). Progression-free survival in the W/M group (11.0 weeks) was similar to that in the M/M group (8.0 weeks), and was significantly shorter than in the W/W group (18.0 weeks) (p < 0.002). Conclusion: High-sensitivity KRAS mutation testing is useful for selecting true responders to cetuximab. Copyright (C) 2012 S. Karger AG, Basel