Use of Early Tumor Shrinkage to Predict Long-Term Outcome in Metastatic Colorectal Cancer Treated With Cetuximab
Use of Early Tumor Shrinkage to Predict Long-Term Outcome in Metastatic Colorectal Cancer Treated With Cetuximab
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DOI：
10.1200/jco.2012.42.8532
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发表时间：
2013-10-20
影响因子：
45.3
通讯作者：
Tejpar, Sabine
中科院分区：
文献类型：
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作者：
Piessevaux, Hubert;Buyse, Marc;Tejpar, Sabine
目的接受西妥昔单抗治疗的化疗难治的转移性结直肠癌患者早期肿瘤缩小(ETS)与长期预后相关。在控制了KRAS肿瘤突变状态后，在随机晶体和OPUS mCRC试验的一线设置中研究了这种相关性。方法第8周的放射学评估被用来计算靶区最长直径之和的相对变化。与时间相关的接收器操作特性提供了C-tau指数(与时间相关的c-指数)。COX回归模型和亚群治疗效应图分析研究了8周放射肿瘤体积缩小(ETS)与生存期和无进展生存期(PFS)之间的关系。结果在两个试验中，在KRAS野生型mCRC患者中，接受化疗加西妥昔单抗的患者的PFS和生存期的C tau值高于单独接受化疗的患者(P<；.001)，表明ETS对这些患者的长期预后有更强的预测价值。在Crystal和OPUS试验中，Ets>；=20%(v<；20%)的临界值分别确定了接受化疗加西妥昔单抗的KRAS野生型mCRC患者的PFS(中位数14.1个月至7.3个月，风险比[HR]=0.32；P<；.001，中位数11.9个月至5.7个月，HR=0.22；P<；.001)和生存期(中位数30.0至18.6个月，HR=0.53；P<；；中位数为26.0个月，中位数为15.7个月，HR=0.43；P=.006)。结论ETS与一线化疗加西妥昔单抗治疗的KRAS野生型mCRC患者的长期预后显著相关。需要在前瞻性试验中进行验证，以评估这种治疗中标记物在临床决策过程中的价值。
PurposeEarly tumor shrinkage (ETS) is associated with long-term outcome in patients with chemorefractory metastatic colorectal cancer (mCRC) receiving cetuximab. This association was investigated in the first-line setting in the randomized CRYSTAL and OPUS mCRC trials, after controlling for KRAS tumor mutation status.MethodsRadiologic assessments at week 8 were used to calculate the relative change in the sum of the longest diameters of the target lesions. Time-dependent receiver operating characteristics provided C tau-indices (time-dependent c-index). Cox regression models and subpopulation treatment effect pattern plot analysis investigated associations between ETS (radiologic tumor size decrease at week 8) and survival and progression-free survival (PFS).ResultsIn both trials, in patients with KRAS wild-type mCRC, C tau values for PFS and survival were higher (P < .001) in those receiving chemotherapy plus cetuximab versus chemotherapy alone, indicating a stronger predictive value of ETS for long-term outcome in these patients. In the CRYSTAL and OPUS trials, respectively, the cutoff value of ETS >= 20% (v < 20%) identified patients with KRAS wild-type mCRC receiving chemotherapy plus cetuximab with longer PFS (medians 14.1 v 7.3 months, hazard ratio [HR] = 0.32; P < .001, and medians 11.9 v 5.7 months, HR = 0.22; P < .001) and survival (medians 30.0 v 18.6 months, HR = 0.53; P < .001 and medians 26.0 v 15.7 months, HR = 0.43; P = .006).ConclusionETS was significantly associated with long-term outcome in patients with KRAS wild-type mCRC treated first-line with chemotherapy plus cetuximab. Validation in prospective trials is required to assess the value of this on-treatment marker in the clinical decision-making process.