Prognostic Value of Liver Metastases and KRAS Mutations in Patients With Metastatic Colorectal Cancer: A Pooled Analysis of Third-Line Placebo-Controlled Trials From the ARCAD CRC Database

IF 2.7 3区医学 Q2 ONCOLOGY

Clinical colorectal cancer Pub Date : 2026-09-01 Epub Date: 2026-05-25 DOI:10.1016/j.clcc.2026.05.007

Thomas Samaille, Morteza Raeisi, Romain Cohen, Qian Shi, Takayuki Yoshino, John R. Zalcberg, Richard Adams, Chiara Cremolini, Axel Grothey, Robert J. Mayer, Benoist Chibaudel, Aimery de Gramont, Thierry André

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引用次数: 0

Abstract

Background

KRAS mutations in metastatic colorectal cancer (mCRC) are a factor of poor prognosis, partly because of associated resistance to anti-EGFR therapies. Liver metastases (LM) were also described as a factor of poor prognosis. This study aims to compare the outcomes of patients treated in third-line setting with placebo or Trifluridine/Tipiracil or regorafenib (TToR) and to assess the impact of LM and KRAS mutations on prognosis.

Methods

Data were pooled from five placebo-controlled randomized trials of the ARCAD CRC database (CORRECT, RECOURSE, CONCUR, TERRA, and J003). Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan–Meier estimates and adjusted Cox models. Interaction tests were conducted to evaluate the combined effects of LM and KRAS mutations.

Results

The study included 2,207 patients: 1,464 treated with TToR and 743 with placebo. A total of 73% had LM and 51% had KRAS mutations. Patients with LM had significantly lower OS and PFS compared to those without LM in both TToR (HR = 0.48 for OS; HR = 0.55 for PFS) and placebo groups (HR = 0.49 for OS; HR = 0.58 for PFS). Patients with KRAS mutations had worse OS compared to wild-type KRAS in TToR-treated patients (HR = 1.18), but not in placebo-treated patients (HR = 1.03). Interaction tests were not significant between LM and KRAS status in both TToR and placebo groups.

Conclusions

In patients with refractory mCRC, LM are a major poor prognosis factor, while KRAS mutations have no clinically relevant additive impact. These results underline the importance to stratify clinical trials on liver metastases rather than on RAS status in latter lines.

查看原文本刊更多论文

肝转移和KRAS突变在转移性结直肠癌患者中的预后价值：来自ARCAD CRC数据库的三线安慰剂对照试验的汇总分析

背景：KRAS突变在转移性结直肠癌（mCRC）中是一个预后不良的因素，部分原因是与抗egfr治疗相关的耐药性。肝转移（LM）也被认为是预后不良的一个因素。本研究旨在比较三线治疗中使用安慰剂或Trifluridine/Tipiracil或regorafenib （tor）的患者的预后，并评估LM和KRAS突变对预后的影响。方法：数据来自ARCAD CRC数据库的5个安慰剂对照随机试验（CORRECT、resource、CONCUR、TERRA和J003）。使用Kaplan-Meier估计和调整后的Cox模型分析总生存期（OS）和无进展生存期（PFS）。相互作用试验评估LM和KRAS突变的联合效应。结果：该研究包括2207名患者：1464名患者接受了tor治疗，743名患者接受了安慰剂治疗。共有73%的人有LM， 51%的人有KRAS突变。在tor组（OS组HR = 0.48， PFS组HR = 0.55）和安慰剂组（OS组HR = 0.49， PFS组HR = 0.58）中，LM患者的OS和PFS均显著低于无LM患者。与野生型KRAS相比，tor治疗的KRAS突变患者的OS更差（HR = 1.18），而安慰剂治疗的患者则没有这种情况（HR = 1.03）。在tor组和安慰剂组中，LM和KRAS状态之间的相互作用试验无显著性差异。结论：在难治性mCRC患者中，LM是主要的不良预后因素，而KRAS突变没有临床相关的附加影响。这些结果强调了对肝转移进行分层临床试验的重要性，而不是对后几系的RAS状态进行分层。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical colorectal cancer 医学-肿瘤学

CiteScore

5.50

自引率

2.90%

发文量

审稿时长

27 days

期刊介绍： Clinical Colorectal Cancer is a peer-reviewed, quarterly journal that publishes original articles describing various aspects of clinical and translational research of gastrointestinal cancers. Clinical Colorectal Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of colorectal, pancreatic, liver, and other gastrointestinal cancers. The main emphasis is on recent scientific developments in all areas related to gastrointestinal cancers. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.