KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab
KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab
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DOI：
10.1200/jco.2007.12.5906
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发表时间：
2008-01-20
影响因子：
45.3
通讯作者：
Laurent-Puig, Pierre
中科院分区：
文献类型：
--
作者：
Lievre, Astrid;Bachet, Jean-Baptiste;Laurent-Puig, Pierre
目的西妥昔单抗（Cetuximab）治疗晚期结直肠癌（CRC）疗效显著。我们先前发现，KRAS突变与30例CRC患者对西妥昔单抗的耐药相关。本研究的目的是验证，在一个独立的较大系列的89例患者，KRAS突变对西妥昔单抗和survival.Patients和方法的预后价值西妥昔单抗治疗失败后与伊立替康为基础的化疗89转移性CRC患者进行了分析KRAS突变的等位基因歧视肿瘤DNA。分析KRAS突变与肿瘤缓解、皮肤毒性、无进展生存期（PFS）和总生存期（OS）之间的关系。结果27%的患者存在KRAS突变，且与西妥昔单抗耐药相关（在24例突变和65例非突变患者中，应答者分别为0%和40%; P =.001），（无突变患者的中位PFS：10.1 vs 31.4周; P =.0001;无突变患者的中位OS：10.1 vs 14.3个月; P =.026）。当我们将这89例患者与我们先前研究的患者合并时，多变量分析显示KRAS状态是与OS和PFS相关的独立预后因素，而皮肤毒性仅与OS相关。结论这些结果证实了KRAS突变对西妥昔单抗治疗转移性结直肠癌患者的反应和生存的高预后价值。
Purpose Cetuximab is efficient in advanced colorectal cancer (CRC). We previously showed that KRAS mutations were associated with resistance to cetuximab in 30 CRC patients. The aim of this study was to validate, in an independent larger series of 89 patients, the prognostic value of KRAS mutations on response to cetuximab and survival.Patients and Methods Eighty-nine metastatic CRC patients treated with cetuximab after treatment failure with irinotecan-based chemotherapy were analyzed for KRAS mutation by allelic discrimination on tumor DNA. The association between KRAS mutations and tumor response, skin toxicity, progression-free survival (PFS) and overall survival ( OS) was analyzed.Results A KRAS mutation was present in 27% of the patients and was associated with resistance to cetuximab (0% v 40% of responders among the 24 mutated and 65 nonmutated patients, respectively; P =.001) and a poorer survival ( median PFS: 10.1 v 31.4 weeks in patients without mutation; P =.0001; median OS: 10.1 v 14.3 months in patients without mutation; P =.026). When we pooled these 89 patients with patients from our previous study, the multivariate analysis showed that KRAS status was an independent prognostic factor associated with OS and PFS, whereas skin toxicity was only associated with OS. In a combined analysis, median OS times of patients with two, one, or no favorable prognostic factors ( severe skin toxicity and no KRAS mutation) was of 15.6, 10.7, and 5.6 months, respectively.Conclusion These results confirm the high prognostic value of KRAS mutations on response to cetuximab and survival in metastatic CRC patients treated with cetuximab.