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基线 ctDNA 基因突变作为转移性结直肠癌使用帕尼单抗和化疗后生存的生物标志物。

Baseline ctDNA gene alterations as a biomarker of survival after panitumumab and chemotherapy in metastatic colorectal cancer.

机构信息

Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.

Department of Immunology, Nagoya University Graduate School of Medicine, Aichi, Japan.

出版信息

Nat Med. 2024 Mar;30(3):730-739. doi: 10.1038/s41591-023-02791-w. Epub 2024 Feb 12.

DOI:10.1038/s41591-023-02791-w
PMID:38347302
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10957476/
Abstract

Certain genetic alterations and right-sided primary tumor location are associated with resistance to anti-epidermal growth factor (EGFR) treatment in metastatic colorectal cancer (mCRC). The phase 3 PARADIGM trial (n = 802) demonstrated longer overall survival with first-line anti-EGFR (panitumumab) versus antivascular endothelial growth factor (bevacizumab) plus modified FOLFOX6 in patients with RAS wild-type mCRC with left-sided primary tumors. This prespecified exploratory biomarker analysis of PARADIGM (n = 733) evaluated the association between circulating tumor DNA (ctDNA) gene alterations and efficacy outcomes, focusing on a broad panel of gene alterations associated with resistance to EGFR inhibition, including KRAS, NRAS, PTEN and extracellular domain EGFR mutations, HER2 and MET amplifications, and ALK, RET and NTRK1 fusions. Overall survival was prolonged with panitumumab plus modified FOLFOX6 versus bevacizumab plus modified FOLFOX6 in patients with ctDNA that lacked gene alterations in the panel (that is, negative hyperselected; median in the overall population: 40.7 versus 34.4 months; hazard ratio, 0.76; 95% confidence interval, 0.62-0.92) but was similar or inferior with panitumumab in patients with ctDNA that contained any gene alteration in the panel (19.2 versus 22.2 months; hazard ratio, 1.13; 95% confidence interval, 0.83-1.53), regardless of tumor sidedness. Negative hyperselection using ctDNA may guide optimal treatment selection in patients with mCRC. ClinicalTrials.gov registrations: NCT02394834 and NCT02394795 .

摘要

某些基因改变和右侧原发性肿瘤位置与转移性结直肠癌（mCRC）患者对表皮生长因子（EGFR）治疗的耐药性有关。III 期 PARADIGM 试验（n=802）表明，对于左侧原发性肿瘤的 RAS 野生型 mCRC 患者，一线抗 EGFR（帕尼单抗）与抗血管内皮生长因子（贝伐单抗）加改良 FOLFOX6 相比，总生存期更长。该 PARADIGM 的预先指定的探索性生物标志物分析（n=733）评估了循环肿瘤 DNA（ctDNA）基因改变与疗效结果之间的关系，重点关注与 EGFR 抑制耐药相关的广泛基因改变，包括 KRAS、NRAS、PTEN 和细胞外结构域 EGFR 突变、HER2 和 MET 扩增以及 ALK、RET 和 NTRK1 融合。在 ctDNA 中缺乏该面板基因改变的患者（即阴性超选择）中，panitumumab 联合改良 FOLFOX6 与 bevacizumab 联合改良 FOLFOX6 相比，总生存期延长（总体人群中位数：40.7 与 34.4 个月；风险比，0.76；95%置信区间，0.62-0.92），但在 ctDNA 中包含该面板任何基因改变的患者中，panitumumab 相似或劣效（19.2 与 22.2 个月；风险比，1.13；95%置信区间，0.83-1.53），与肿瘤侧别无关。使用 ctDNA 进行阴性超选择可能有助于指导 mCRC 患者的最佳治疗选择。ClinicalTrials.gov 注册号：NCT02394834 和 NCT02394795。

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1
Clinical Validation of Plasma-Based Genotyping for and V600E Mutation in Metastatic Colorectal Cancer: SCRUM-Japan GOZILA Substudy.基于血浆的种系基因检测在转移性结直肠癌和 V600E 突变中的临床验证：SCRUM-Japan GOZILA 子研究。
JCO Precis Oncol. 2023 Jun;7:e2200688. doi: 10.1200/PO.22.00688.
2
Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with metastatic colorectal cancer.泛亚地区适应的 ESMO 临床实践指南：转移性结直肠癌患者的诊断、治疗和随访。
ESMO Open. 2023 Jun;8(3):101558. doi: 10.1016/j.esmoop.2023.101558. Epub 2023 May 24.
3
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Front Immunol. 2025 Aug 8;16:1631620. doi: 10.3389/fimmu.2025.1631620. eCollection 2025.
4
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5
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ESMO Open. 2025 Jun 23;10(7):105491. doi: 10.1016/j.esmoop.2025.105491.
6
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帕尼单抗联合贝伐珠单抗对比标准一线化疗方案联合贝伐珠单抗用于 RAS 野生型、左侧转移性结直肠癌患者的生存获益：一项随机临床试验。
JAMA. 2023 Apr 18;329(15):1271-1282. doi: 10.1001/jama.2023.4428.
4
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Cancers (Basel). 2022 Dec 9;14(24):6075. doi: 10.3390/cancers14246075.
5
Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up.转移性结直肠癌：ESMO 诊断、治疗及随访临床实践指南
Ann Oncol. 2023 Jan;34(1):10-32. doi: 10.1016/j.annonc.2022.10.003. Epub 2022 Oct 25.
6
Treatment of Metastatic Colorectal Cancer: ASCO Guideline.转移性结直肠癌的治疗：ASCO 指南。
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7
Good Publication Practice (GPP) Guidelines for Company-Sponsored Biomedical Research: 2022 Update.良好的出版实践（GPP）指南：公司赞助的生物医学研究：2022 更新版。
Ann Intern Med. 2022 Sep;175(9):1298-1304. doi: 10.7326/M22-1460. Epub 2022 Aug 30.
8
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Oncologist. 2021 Nov;26(11):e1971-e1981. doi: 10.1002/onco.13905. Epub 2021 Aug 4.
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