Marković Filip, Milin-Lazović Jelena, Nikolić Nikola, Golubović Aleksa, Stjepanović Mihailo, Kontić Milica
Clinic for Pulmonology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia.
Department for Medical Statistics and Informatics, School of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
Curr Oncol. 2025 Jun 19;32(6):365. doi: 10.3390/curroncol32060365.
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 I 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.
近期研究表明KRAS突变与免疫检查点抑制剂（ICI）的疗效之间存在关联，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。这些突变可增加肿瘤突变负荷（TMB）和新抗原负荷，可能导致对ICI的反应改善。本荟萃分析旨在整合现有证据，探讨KRAS突变作为接受ICI治疗的晚期非小细胞肺癌（NSCLC）患者生存和治疗结果预测因素的影响。由一名生物统计学家和一名肺科医生设计了全面的检索策略，检索截至2022年5月的PubMed、科学网和Scopus数据库。评估的结局包括总生存期（OS）和无进展生存期（PFS），以对数风险比（HR）及相应的标准误（SE）报告。使用Review Manager（RevMan，Cochrane协作网，英国伦敦）计算HR效应大小的合并估计值。使用Cochran Q检验和I统计量评估研究间的异质性。最终，在总共8722篇筛选的标题和摘要中，有10篇文章被认为适合纳入系统评价。KRAS+突变的存在是接受检查点抑制剂治疗的NSCLC患者OS更好的显著预后因素（HR = 0.89，95%CI：0.79 - 0.99），也是接受检查点抑制剂治疗的NSCLC患者PFS更好的显著预后因素（HR = 0.72，95%CI：0.59 - 0.87）。总之，我们的研究表明，KRAS突变可能是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潜在的阳性预测生物标志物。
