Association of k-ras mutational status and clinical outcomes in patients with metastatic colorectal. cancer receiving panitumumab alone
Association of k-ras mutational status and clinical outcomes in patients with metastatic colorectal. cancer receiving panitumumab alone
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DOI：
10.3816/ccc.2008.n.024
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发表时间：
2008-05-01
影响因子：
3.4
通讯作者：
Amado, Rafael G.
中科院分区：
文献类型：
--
作者：
Freeman, Daniel J.;Juan, Todd;Amado, Rafael G.
背景：识别预测生物标志物对于优化治疗患者非常重要。该分析评估了 K-ras、BRAF 和 PIK3CA 基因突变与肿瘤对帕尼单抗单独耐药的关联。患者和方法：从 3 期 11 帕尼单抗转移性结直肠癌 (mCRC) 研究中，获得了 533 名患者样本中的 62 名。通过测序从基因组 DNA 中鉴定出突变。结果：62个样本中，24个（38.7%）存在K-ras突变，38个（61.3%）为野生型。在野生型 K-ras 组中，11% 的患者出现部分缓解 (PR)，53% 的患者病情稳定 (SD)，37% 的患者出现疾病进展 (PD)。在突变K-ras组中，21%的患者患有SD，79%的患者患有PD；没有任何反应。 K-ras 突变的缺失与帕尼单抗的反应相关（PR vs. SD vs. PD；P=.0028）。野生型与突变型 K-ras 的无进展生存风险比为 0.4 (95% Cl, 0.2-0.7)，总生存风险比为 0.5 (95% Cl, 0.3-0.9)。 4 名患者存在 V600E BRAF 突变，2 名患者存在 PIK3CA 突变。结论：这些数据表明，具有激活 K-ras 突变的转移性结直肠癌患者不太可能对单独的帕尼单抗产生反应。小样本量限制了我们定义 PIK3CA 和 BRAF 突变对帕尼单抗治疗的预测作用。
Background: Identifying predictive biomarkers is important to optimally treat patients. This analysis evaluated the association of K-ras,BRAF,and PIK3CA gene mutations with tumor resistance to panitumumab alone. Patients and Methods: From 3 phase 11 panitumumab metastatic colorectal cancer (mCRC) studies, 62 of 533 patient samples were available. Mutations were identified from genomic DNA by sequencing. Results: Of the 62 samples, 24 (38.7%) harbored a K-ras mutation, and 38 (61.3%) were wild type. In the wild-type K-ras group, 11% of patients had a partial response (PR), 53% had stable disease (SD), and 37% had progressive disease (PD). In the mutant K-ras group, 21% of patients had SD, and 79% of patients had PD; there were no responses. The absence of a K-ras mutation was associated with response to panitumumab (PR vs. SD vs. PD; P=.0028). The hazard ratio for wild-type versus mutant K-ras was 0.4 (95% Cl, 0.2-0.7) for progression-free survival and 0.5 (95% Cl, 0.3-0.9) for overall survival. Four patients had aV600E BRAF mutation, and 2 patients had a PIK3CA mutation. Conclusion: These data suggest that patients with mCRC with activating K-ras mutations are less likely to respond to panitumumab alone. The small sample size limits us from defining a predictive role of PIK3CA and BRAF mutations for panitumumab treatment.