KRAS Mutations as Predictive Biomarkers for First-Line Immune Checkpoint Inhibitor Monotherapy in Advanced NSCLC: A Systematic Review and Meta-Analysis.

IF 2.8 4区 医学 Q2 ONCOLOGY
Filip Marković, Jelena Milin-Lazović, Nikola Nikolić, Aleksa Golubović, Mihailo Stjepanović, Milica Kontić
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引用次数: 0

Abstract

Recent research suggests a link between KRAS mutations and the effectiveness of ICIs, as KRAS-driven tumors may possess unique immunogenic features that influence the tumor microenvironment. These mutations can increase tumor mutation burden (TMB) and neoantigen load, potentially leading to improved responses to ICIs. This meta-analysis aims to consolidate existing evidence on the impact of KRAS mutations as a predictive factor for survival and treatment outcomes in patients with advanced NSCLC treated with ICIs. A comprehensive search strategy was designed by a biostatistician and pulmonologist, targeting PubMed, Web of Science, and Scopus databases up to May 2022. The outcomes assessed included overall survival (OS) and progression-free survival (PFS), reported as log hazard ratios (HRs) with corresponding standard errors (SEs). A pooled estimate of the HR effect size was calculated using Review Manager (RevMan, Cochrane Collaboration, London, UK). Heterogeneity among studies was evaluated using the Cochran Q test and the I2 statistic. Ultimately, 10 articles were deemed suitable for inclusion in the systematic review from a total of 8722 screened titles and abstracts. The presence of KRAS+ mutations had a significant prognostic factor for better OS in NSCLC patients treated with checkpoint inhibitors (HR = 0.89, 95% CI: 0.79-0.99) and for better PFS in NSCLC patients treated with checkpoint inhibitors (HR = 0.72, 95% CI: 0.59-0.87). In conclusion, our study indicates that KRAS mutations may serve as a potential positive predictive biomarker in patients with advanced non-small-cell lung cancer treated with immune checkpoint inhibitor monotherapy.

KRAS突变作为晚期非小细胞肺癌一线免疫检查点抑制剂单药治疗的预测性生物标志物:系统回顾和荟萃分析
最近的研究表明,KRAS突变与ICIs的有效性之间存在联系,因为KRAS驱动的肿瘤可能具有影响肿瘤微环境的独特免疫原性特征。这些突变可以增加肿瘤突变负荷(TMB)和新抗原负荷,可能导致对ICIs的反应改善。本荟萃分析旨在巩固KRAS突变作为晚期NSCLC患者接受ICIs治疗的生存和治疗结果预测因素影响的现有证据。由一位生物统计学家和肺科学家设计了一个全面的搜索策略,目标是PubMed, Web of Science和Scopus数据库,截止到2022年5月。评估的结果包括总生存期(OS)和无进展生存期(PFS),以对数风险比(hr)和相应的标准误差(SEs)报告。使用Review Manager (RevMan, Cochrane Collaboration,伦敦,英国)计算了人力资源效应大小的汇总估计。采用Cochran Q检验和I2统计量评估研究间的异质性。最终,从8722篇筛选的题目和摘要中筛选出10篇文章,认为适合纳入系统评价。KRAS+突变的存在对于接受检查点抑制剂治疗的NSCLC患者更好的OS (HR = 0.89, 95% CI: 0.79-0.99)和接受检查点抑制剂治疗的NSCLC患者更好的PFS (HR = 0.72, 95% CI: 0.59-0.87)具有重要的预后因素。总之,我们的研究表明,KRAS突变可能在接受免疫检查点抑制剂单药治疗的晚期非小细胞肺癌患者中作为潜在的阳性预测生物标志物。
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
Current oncology
Current oncology ONCOLOGY-
CiteScore
3.30
自引率
7.70%
发文量
664
审稿时长
1 months
期刊介绍: Current Oncology is a peer-reviewed, Canadian-based and internationally respected journal. Current Oncology represents a multidisciplinary medium encompassing health care workers in the field of cancer therapy in Canada to report upon and to review progress in the management of this disease. We encourage submissions from all fields of cancer medicine, including radiation oncology, surgical oncology, medical oncology, pediatric oncology, pathology, and cancer rehabilitation and survivorship. Articles published in the journal typically contain information that is relevant directly to clinical oncology practice, and have clear potential for application to the current or future practice of cancer medicine.
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