Comprehensive Genome Profiling for Treatment Decisions in Patients with Metastatic Tumors: Real-World Evidence Meta-Analysis and Registry Data Implementation

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

Background Although precision oncology has rapidly been developed in recent years, its real-world impact and challenges in healthcare implementation remain underexplored. Through a meta-analysis of real-world evidence (RWE), we aimed at investigating the applicability and clinical impact of comprehensive cancer 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% Confidence Interval (CI) 13.4-18.2%) of them having received targeted therapy. Objective response was seen in 23.9% (95% CI 20.8-27.3%). Overall, CGP-guided treatment was correlated with prolonged progression-free survival (pooled Hazard Ratio (HR) = 0.63; 95% CI, 0.56-0.70; 18 studies) and overall survival (pooled HR = 0.60; 95% CI, 0.51-0.70; 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 healthcare strategies.
转移性肿瘤患者治疗决策的综合基因组谱分析:真实世界证据荟萃分析和注册数据实施
尽管近年来精确肿瘤学发展迅速,但其在医疗保健实施中的现实影响和挑战仍未得到充分探讨。通过真实世界证据(RWE)的荟萃分析,我们旨在探讨综合癌症基因组谱(CGP)在转移性实体瘤癌症患者中的适用性和临床影响。方法我们系统地检索Medline、Embase和Web of Science关于转移性实体瘤中CGP和匹配疗法的RWE研究(发表期:2012-2023)。计算可操作的基因组改变、接受匹配靶向治疗的患者、治疗和生存结果的合并比例。来自瑞典癌症登记处的数据被用作全国CGP实施的案例研究。结果在7218项确定的研究中,144项纳入我们的分析。59.8%的cgp检测患者有可操作的基因组改变,其中15.6%(95%置信区间(CI) 13.4-18.2%)的患者接受了靶向治疗。客观缓解率为23.9% (95% CI 20.8-27.3%)。总体而言,cgp引导治疗与延长无进展生存期相关(合并风险比(HR) = 0.63;95% ci, 0.56-0.70;18项研究)和总生存率(合并HR = 0.60;95% ci, 0.51-0.70;21项研究),与常规治疗相比。元回归时间预测分析表明,到2030年,这些比率将稳步上升。RWE研究的汇总分析表明,大约四分之一接受cgp匹配治疗的患者有客观反应。通过利用meta回归预测,我们的全国癌症登记案例研究为转移性癌症患者提供了精确肿瘤学潜力的见解,并为未来的医疗保健策略提供了信息。
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