KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab
KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab
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DOI：
10.1093/annonc/mdm496
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发表时间：
2008-03-01
影响因子：
50.5
通讯作者：
Tejpar, S.
中科院分区：
文献类型：
--
作者：
De Roock, W.;Piessevaux, H.;Tejpar, S.
背景资料：KRAS突变状态是预测接受西妥昔单抗（CTX）治疗的转移性结直肠癌（mCRC）患者生存期的候选标志物。患者和方法：我们在临床试验中研究了113例接受CTX治疗的伊立替康难治性mCRC患者的KRAS突变状态。采用Logistic和考克斯回归分析建立客观缓解（OR）、无进展生存期（PFS）和总生存期（OS）的预测模型。结果：66例KRAS野生型（WT）患者中有27例出现OR，而KRAS突变型患者中42例无OR。KRAS WT的中位OS显著优于突变体（43.0 vs 27.3周; P = 0.020）。WT患者在所有时间点的肿瘤大小减小显著更大。与所有其他患者相比，第6周肿瘤大小初始相对减小> 9.66%的KRAS WT患者的中位OS显著更好（74.9 vs 30.6周; P = 0.0000025）。在KRAS WT患者中，初始下降的患者OS显著优于未下降的患者[中位OS：74.9 vs 30.6周（P = 0.00000012）]。结论：KRAS WT状态与CTX治疗的mCRC的生存获益相关。这种益处在早期放射学反应的患者中更为明显。这些特征可用于响应预测。
Background: KRAS mutation status is a candidate marker for predicting survival in patients with metastatic colorectal cancer (mCRC) treated with cetuximab (CTX).Patients and methods: We studied the KRAS mutation status of 113 patients with irinotecan refractory mCRC treated with CTX in clinical trials. A predictive model for objective response (OR), progression-free survival (PFS) and overall survival (OS) was constructed using logistic and Cox regression.Results: OR was seen in 27 of 66 KRAS wild-type (WT) patients versus 0 of 42 in KRAS mutants. Median OS was significantly better in KRAS WT versus mutants (43.0 versus 27.3 weeks; P = 0.020). Decrease in tumor sizes was significantly larger at all time points in WT patients. KRAS WT patients with an initial relative decrease of tumor size > 9.66% at week 6 had a significantly better median OS compared with all other patients (74.9 versus 30.6 weeks; P = 0.0000025). Within KRAS WT patients OS was significantly better in patients with an initial decrease compared with those without [median OS: 74.9 versus 30.6 weeks (P = 0.00000012)].Conclusions: KRAS WT status is associated to survival benefit in CTX treated mCRC. This benefit is even more pronounced in those patients with early radiological response. These characteristics may be exploited for response prediction.