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转移性肿瘤患者治疗决策的综合基因组分析:真实世界证据的荟萃分析及登记数据的应用

Comprehensive genome profiling for treatment decisions in patients with metastatic tumors: real-world evidence meta-analysis and registry data implementation.

作者信息

Zerdes Ioannis, Filis Panagiotis, Fountoukidis Georgios, El-Naggar Ali Inan, Kalofonou Foteini, D'Alessio Antonio, Pouptsis Athanasios, Foukakis Theodoros, Pentheroudakis George, Ahlgren Johan, Smith Daniel, Valachis Antonios

机构信息

Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.

Theme Cancer, Karolinska University Hospital and Comprehensive Cancer Center, Stockholm, Sweden.

出版信息

J Natl Cancer Inst. 2025 Jun 1;117(6):1117-1124. doi: 10.1093/jnci/djaf015.

DOI:10.1093/jnci/djaf015
PMID:39842854
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12145917/
Abstract

BACKGROUND

Although precision oncology has rapidly been developed in recent years, its real-world impact and challenges in health care implementation remain underexplored. Through a meta-analysis of real-world evidence (RWE), we aimed at investigating the applicability and clinical impact of comprehensive genome profiling (CGP) in cancer patients with metastatic solid tumors.

METHODS

We systematically searched Medline, Embase, and Web of Science for RWE studies on CGP and matched therapies in metastatic solid tumors (publication period: 2012-2023). Pooled proportions of actionable genomic alterations, patients treated with matched targeted therapies, treatment, and survival outcomes were calculated. Data from Swedish cancer registries were used as a case study for nationwide CGP implementation.

RESULTS

Out of the 7218 identified studies, 144 were included in our analysis; 59.8% of CGP-tested patients had actionable genomic alterations, with 15.6% (95% CI = 13.4% to 18.2%) of them having received targeted therapy. Objective response was seen in 23.9% (95% CI = 20.8% to 27.3%). Overall, CGP-guided treatment was correlated with prolonged progression-free survival (pooled hazard ratio [HR] = 0.63; 95% CI = 0.56 to 0.70; 18 studies) and overall survival (pooled HR = 0.60; 95% CI = 0.51 to 0.70; 21 studies) when compared to conventional treatment. Meta-regression time projections analyses showed that these rates will steadily increase by 2030.

CONCLUSIONS

Pooled analyses of RWE studies indicate that approximately one-fourth of the patients receiving CGP-matched treatment have an objective response. By utilizing meta-regression projections, our nationwide cancer registry case study offers insights into the potential of precision oncology for patients with metastatic cancer and to inform future health care strategies.

摘要

背景

尽管近年来精准肿瘤学发展迅速,但其在医疗保健实施中的实际影响和挑战仍未得到充分探索。通过对真实世界证据(RWE)的荟萃分析,我们旨在研究综合基因组分析(CGP)在转移性实体瘤癌症患者中的适用性和临床影响。

方法

我们系统检索了Medline、Embase和Web of Science上关于CGP和转移性实体瘤匹配疗法的RWE研究(发表时间:2012 - 2023年)。计算了可操作基因组改变的合并比例、接受匹配靶向疗法治疗的患者比例、治疗情况和生存结果。来自瑞典癌症登记处的数据被用作全国范围内实施CGP的案例研究。

结果

在7218项已识别的研究中,144项被纳入我们的分析;接受CGP检测的患者中有59.8%存在可操作的基因组改变,其中15.6%(95%置信区间 = 13.4%至18.2%)接受了靶向治疗。客观缓解率为23.9%(95%置信区间 = 20.8%至27.3%)。总体而言,与传统治疗相比,CGP指导的治疗与无进展生存期延长相关(合并风险比[HR] = 0.63;95%置信区间 = 0.56至0.70;18项研究)和总生存期延长相关(合并HR = 0.60;95%置信区间 = 0.51至0.70;21项研究)。Meta回归时间预测分析表明,到2030年这些比率将稳步上升。

结论

RWE研究的汇总分析表明,接受CGP匹配治疗的患者中约四分之一有客观缓解。通过利用Meta回归预测,我们的全国癌症登记处案例研究为转移性癌症患者的精准肿瘤学潜力提供了见解,并为未来的医疗保健策略提供信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56cc/12145917/016873eaf1ff/djaf015f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56cc/12145917/7eb6401c16cd/djaf015f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56cc/12145917/016873eaf1ff/djaf015f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56cc/12145917/7eb6401c16cd/djaf015f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56cc/12145917/016873eaf1ff/djaf015f2.jpg

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本文引用的文献

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The ESMO Tumour-Agnostic Classifier and Screener (ETAC-S): a tool for assessing tumour-agnostic potential of molecularly guided therapies and for steering drug development.ESMO 肿瘤不可知分类器和筛查器(ETAC-S):一种用于评估基于分子靶向治疗的肿瘤不可知性和指导药物开发的工具。
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Clin Exp Med. 2024 Apr 10;24(1):73. doi: 10.1007/s10238-024-01336-w.
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If it's a target, it's a pan-cancer target: Tissue is not the issue.如果是靶点,那就是泛癌靶点:组织不是问题。
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