Impact of Consensus Molecular Subtype on Survival in Patients With Metastatic Colorectal Cancer: Results From CALGB/SWOG 80405 (Alliance)
Impact of Consensus Molecular Subtype on Survival in Patients With Metastatic Colorectal Cancer: Results From CALGB/SWOG 80405 (Alliance)
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DOI：
10.1200/jco.18.02258
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发表时间：
2019-08-01
影响因子：
45.3
通讯作者：
Kabbarah, Omar
中科院分区：
文献类型：
--
作者：
Lenz, Heinz-Josef;Ou, Fang-Shu;Kabbarah, Omar
[中英文摘要]为了确定结直肠癌共有的分子亚型(CMS)的预测和预后价值，为CALGB/SWOG 80405登记的患者提供一个框架，捕捉结直肠癌的内在异质性。这些CMS代表了来自六个独立分类系统的主要基于原发肿瘤的基因表达特征。PATIENTS和METHSCALGB/SWOG 80405是一项III期试验，比较了加入贝伐单抗或西妥昔单抗与输注氟尿嘧啶、亚叶酸钙、奥沙利铂或氟尿嘧啶、亚叶酸钙和伊立替康作为一线治疗晚期结直肠癌的疗效。我们使用一种新的纳米串基因表达板对581名参加研究的患者的原发癌进行CMS分类，以评估CMS在这些患者中的预后和预测价值。结果CMS对总生存期(OS；P<；.001)和无进展生存期(PFS；P<；.001)具有高度的预后意义。此外，CMS对OS(交互作用的P=.001)和PFS(交互作用的P=0.0032)都有预测作用。在CMS1队列中，贝伐单抗治疗的患者的OS显著长于西妥昔单抗治疗的患者(P<；.001)。在CMS2队列中，接受西妥昔单抗治疗的患者的OS显著长于接受贝伐单抗治疗的患者(P=.0046)。结论这些发现突出了CMSS的潜在临床效用，并表明CMS分类的改进可能提供一种途径，以确定哪些转移性结直肠癌患者最有可能从作为初始治疗一部分的特定靶向治疗中受益。
PURPOSETo determine the predictive and prognostic value of the consensus molecular subtypes (CMSs) of colorectal cancer (CRC) that represent a merging of gene expression-based features largely in primary tumors from six independent classification systems and provide a framework for capturing the intrinsic heterogeneity of CRC in patients enrolled in CALGB/SWOG 80405.PATIENTS AND METHODSCALGB/SWOG 80405 is a phase III trial that compared the addition of bevacizumab or cetuximab to infusional fluorouracil, leucovorin, and oxaliplatin or fluorouracil, leucovorin, and irinotecan as first-line treatment of advanced CRC. We characterized the CMS classification using a novel NanoString gene expression panel on primary CRCs from 581 patients enrolled in this study to assess the prognostic and predictive value of CMSs in these patients.RESULTSThe CMSs are highly prognostic for overall survival (OS; P < .001) and progression-free survival (PFS; P < .001). Furthermore, CMSs were predictive for both OS (P for interaction < .001) and PFS (P for interaction = .0032). In the CMS1 cohort, patients treated with bevacizumab had a significantly longer OS than those treated with cetuximab (P < .001). In the CMS2 cohort, patients treated with cetuximab had a significantly longer OS than patients treated with bevacizumab (P = .0046).CONCLUSIONThese findings highlight the possible clinical utility of CMSs and suggests that refinement of the CMS classification may provide a path toward identifying patients with metastatic CRC who are most likely to benefit from specific targeted therapy as part of the initial treatment.