表皮调节素基因表达作为西妥昔单抗治疗晚期结直肠癌获益的生物标志物。
Epiregulin gene expression as a biomarker of benefit from cetuximab in the treatment of advanced colorectal cancer.
机构信息
The Ottawa Hospital Research Institute, University of Ottawa, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada.
Flinders Medical Centre and Flinders University, Flinders Drive, Bedford Park, Adelaide, SA 5042, Australia.
出版信息
Br J Cancer. 2014 Feb 4;110(3):648-55. doi: 10.1038/bjc.2013.753. Epub 2013 Dec 12.
BACKGROUND
Anti-EGFR antibody, cetuximab, improves overall survival (OS) in K-ras wild-type chemotherapy-refractory colorectal cancer. Epidermal growth factor receptor ligand epiregulin (EREG) gene expression may further predict cetuximab benefit.
METHODS
Tumour samples from a phase III clinical trial of cetuximab plus best supportive care (BSC) vs BSC alone (CO.17) were analysed for EREG mRNA gene expression. Predictive effects of high vs low EREG on OS and progression-free survival (PFS) were examined for treatment-biomarker interaction.
RESULTS
Both EREG and K-ras status were ascertained in 385 (193 cetuximab, 192 BSC) tumour samples. Within the high EREG and K-ras wild-type status ('co-biomarker')-positive group (n=139, 36%), median PFS was 5.4 vs 1.9 months (hazard ratio (HR) 0.31; P<0.0001), and median OS was 9.8 vs 5.1 months (HR 0.43; P<0.001) for cetuximab vs BSC, respectively. In the rest (n=246, 64%), PFS (HR 0.82; P=0.12) and OS (HR 0.90; P=0.45) were not significantly different. Test for treatment interaction showed a larger cetuximab effect on OS (HR 0.52; P=0.007) and PFS (HR 0.49; P=0.001) in the co-biomarker-positive group.
CONCLUSION
In pre-treated K-ras wild-type status colorectal cancer, patients with high EREG gene expression appear to benefit more from cetuximab therapy compared with low expression. Epiregulin as a selective biomarker requires further evaluation.
背景
抗表皮生长因子受体抗体西妥昔单抗可提高 K-ras 野生型化疗耐药结直肠癌的总生存期（OS）。表皮生长因子受体配体表皮调节素（EREG）基因表达可能进一步预测西妥昔单抗的获益。
方法
对西妥昔单抗联合最佳支持治疗（BSC）与 BSC 单药治疗（CO.17）的 III 期临床试验的肿瘤样本进行分析，以检测 EREG mRNA 基因表达。为了检测治疗生物标志物的相互作用，评估了高表达与低表达对 OS 和无进展生存期（PFS）的预测效果。
结果
在 385 例（西妥昔单抗 193 例，BSC 192 例）肿瘤样本中均确定了 EREG 和 K-ras 状态。在高 EREG 和 K-ras 野生型状态（“共生物标志物”阳性）组（n=139，36%）中，中位 PFS 为 5.4 与 1.9 个月（风险比（HR）0.31；P<0.0001），中位 OS 为 9.8 与 5.1 个月（HR 0.43；P<0.001），西妥昔单抗与 BSC 相比分别为。在其余患者（n=246，64%）中，PFS（HR 0.82；P=0.12）和 OS（HR 0.90；P=0.45）无显著差异。治疗相互作用检验显示，在共生物标志物阳性组中，西妥昔单抗对 OS（HR 0.52；P=0.007）和 PFS（HR 0.49；P=0.001）的效果更大。
结论
在预处理的 K-ras 野生型结直肠癌中，高 EREG 基因表达的患者似乎比低表达的患者从西妥昔单抗治疗中获益更多。表皮调节素作为一种选择性生物标志物需要进一步评估。
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