摘要

BACKGROUND:FIRE-3 compared first-line therapy with FOLFIRI plus either cetuximab or bevacizumab in 592 KRAS exon 2 wild-type metastatic colorectal cancer (mCRC) patients. The consensus molecular subgroups (CMS) are grouping CRC samples according to their gene-signature in four different subtypes. Relevance of CMS for the treatment of mCRC has yet to be defined.
PATIENTS AND METHODS:In this exploratory analysis, patients were grouped according to the previously published tumor CRC-CMSs. Objective response rates (ORR) were compared using chi-square test. Overall survival (OS) and progression-free survival (PFS) times were compared using Kaplan-Meier estimation, log-rank tests. Hazard ratios (HR) were estimated according to the Cox proportional hazard method.
RESULTS:CMS classification could be determined in 438 out of 514 specimens available from the intent-to-treat (ITT) population (n = 592). Frequencies for the remaining 438 samples were as follows: CMS1 (14%), CMS2 (37%), CMS3 (15%), CMS4 (34%). For the 315 RAS wild-type tumors, frequencies were as follows: CMS1 (12%), CMS2 (41%), CMS3 (11%), CMS4 (34%). CMS distribution in right- versus (vs) left-sided primary tumors was as follows: CMS1 (27% versus 11%), CMS2 (28% versus 45%), CMS3 (10% versus 12%), CMS4 (35% versus 32%). Independent of the treatment, CMS was a strong prognostic factor for ORR (P = 0.051), PFS (P < 0.001), and OS (P < 0.001). Within the RAS wild-type population, OS observed in CMS4 significantly favored FOLFIRI cetuximab over FOLFIRI bevacizumab. In CMS3, OS showed a trend in favor of the cetuximab arm, while OS was comparable in CMS1 and CMS2, independent of targeted therapy.
CONCLUSIONS:CMS classification is prognostic for mCRC. Prolonged OS induced by FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab in the FIRE-3 study appears to be driven by CMS3 and CMS4. CMS classification provides deeper insights into the biology to CRC, but at present time has no direct impact on clinical decision-making.The FIRE-3 (AIO KRK-0306) study had been registered at ClinicalTrials.gov: NCT00433927.

译文

背景: FIRE-3 比较了 592 例 KRAS 2 号野生型转移性结直肠癌 (mCRC) 患者的一线治疗与 FOLFIRI 加西妥昔单抗或贝伐珠单抗。共识分子亚组 (CMS) 是根据四种不同亚型的基因特征对 CRC 样本进行分组。CMS 与 mCRC 治疗的相关性尚未确定。
患者和方法: 在这一探索性分析中,根据之前发表的肿瘤 CRC-CMSs 对患者进行分组。客观反应率 (ORR) 采用卡方检验进行比较。使用 Kaplan-Meier 估计、 log-rank 检验比较总生存期 (OS) 和无进展生存期 (PFS)。根据 Cox 比例风险法估计风险比 (HR)。
结果: 在意向治疗 (ITT) 人群中的 438 份样本中,有 514 份可以确定 CMS 分类 (n = 592)。其余 438 个样本的频率如下: CMS1 (14%) 、 CMS2 (37%) 、 CMS3 (15%) 、 CMS4 (34%)。对于 315 个 RAS 野生型肿瘤,频率如下: CMS1 (12%),CMS2 (41%),CMS3 (11%),CMS4 (34%)。CMS 在左侧原发性肿瘤中的分布如下: CMS1 (27% 对 11%),CMS2 (28% 对 45%),CMS3 (10% 对 12%), CMS4 (35% 对 32%)。独立于治疗,CMS 是 ORR (p = 0.051) 、 PFS (p <0.001) 和 OS (p <0.001) 的一个强有力的预后因素。在 RAS 野生型人群中,在 CMS4 中观察到的 OS 明显有利于 FOLFIRI 西妥昔单抗,而不是 FOLFIRI 贝伐单抗。在 CMS3 中,OS 显示出有利于西妥昔单抗组的趋势,而在 CMS1 和 CMS2 中 OS 具有可比性,独立于靶向治疗。
结论: CMS 分类是 mCRC 的预后因素。在 FIRE-3 研究中,FOLFIRI 加西妥昔单抗与 FOLFIRI 加贝伐单抗诱导的 OS 延长似乎是由 CMS3 和 cms4 驱动的。CMS 分类为 CRC 提供了更深入的生物学见解,但目前对临床 decision-making.The FIRE-3 (AIO KRK-0306) 研究没有直接影响,该研究已在 ClinicalTrials.gov: nct00433927 注册。

cetuximab

肿瘤 结肠癌、肺癌、头颈癌 药物
概述  :  

西妥昔单抗(又名IMC-C225,Erbitux),中文商品名为爱必妥。西妥昔单抗为Imclone公司与BMS联合开发。2003年12月首次在瑞士上市,为第一个上市的靶向单克隆抗体。西妥昔单抗是抗EGFR人/鼠嵌合单克隆抗体,它选择性地与表皮生长因子受体结合,在临床前试验中显示对多种肿瘤细胞株具有抗瘤活性。已被证实它对头颈部癌,非小细胞肺癌和结肠癌等多种肿瘤有效。   西妥昔单抗最早在瑞士批准用于对伊立替康标准疗法不再响应的结肠癌患者,2004年2月初被FDA批准上市,与伊立替康

Cetuximab

释    义   n. 西妥昔单抗

例    句   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. 本研究目的是为了确认:在一个独立的更多的89个患者中,KRAS突变对于西妥昔单抗的反应与生存的预测价值。

请扫描右侧二维码,免费查看词汇专业知识背景