Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Department of Pharmacy, Emergency General Hospital Beijing, China.
Clin Respir J. 2024 Apr;18(4):e13745. doi: 10.1111/crj.13745.
Previous studies have shown that immune checkpoint inhibitors can improve the survival of patients with advanced non-small cell lung cancer with KRAS mutations; however, there is a lack of comparisons between treatment regimens associated with immune checkpoint inhibitors, and our study aims to compare several treatment parties to find a more effective treatment regimen.
A comprehensive literature search was conducted across multiple databases, namely PubMed, Web of Science, Embase, and Cochrane Library, to identify relevant studies. The screened studies were thoroughly examined, and data were collected to establish a Bayesian framework. The study focused on two primary endpoints: overall survival (OS) and progression-free survival (PFS). Data analysis and graphical plotting using R software and Revman (version 5.3). It is worth mentioning that the study protocol was registered with the International Prospective Registry for Systematic Reviews, ensuring transparency and adherence to predetermined protocols (CRD42022379595).
In total, our analysis included six RCTs involving 469 patients with KRAS mutations. Among these patients, 224 received chemotherapy, while 245 were treated with immune checkpoint inhibitors. Meta-analysis results showed that the addition of ICIs could significantly improve OS and PFS (0.69, 95% CI 0.55, 0.86; 0.57, 95% CI 0.42, 0.77). The results of the network meta-analysis showed that Pembrolizumab could improve OS (HR 0.42, 95% CI 0.22-0.80) and Pembrolizumab emerged as the most effective treatment option for enhancing OS in patients (SUCRA 65.03%). Additionally, pembrolizumab in combination with chemotherapy showed improvement in PFS (HR 0.47, 95% CI 0.29-0.76).
Our analysis found that among advanced NSCLC patients with KRAS gene mutations, first-line treatment with pembrolizumab alone demonstrated greater efficacy. Similarly, second-line treatment with nivolumab alone was found to be more effective in this patient population. However, the sample size of this study was limited, Therefore, additional clinical data is necessary to validate this finding in subsequent research.
先前的研究表明，免疫检查点抑制剂可改善 KRAS 突变的晚期非小细胞肺癌患者的生存；然而，缺乏免疫检查点抑制剂相关治疗方案的比较，我们的研究旨在比较几种治疗方案，以找到更有效的治疗方案。
通过综合检索多个数据库（包括 PubMed、Web of Science、Embase 和 Cochrane Library），我们进行了全面的文献检索，以识别相关研究。仔细检查了筛选出的研究，并收集数据以建立贝叶斯框架。该研究主要关注两个主要终点：总生存期（OS）和无进展生存期（PFS）。使用 R 软件和 Revman（版本 5.3）进行数据分析和图形绘制。值得一提的是，该研究方案已在国际前瞻性系统评价注册库（International Prospective Registry for Systematic Reviews）中注册，以确保透明度并遵守预定方案（CRD42022379595）。
我们的分析共纳入了 6 项涉及 469 名 KRAS 突变患者的 RCT。其中 224 例接受化疗，245 例接受免疫检查点抑制剂治疗。荟萃分析结果表明，ICI 的加入可显著改善 OS 和 PFS（0.69，95%CI 0.55，0.86；0.57，95%CI 0.42，0.77）。网络荟萃分析结果显示，Pembrolizumab 可改善 OS（HR 0.42，95%CI 0.22-0.80），并且 Pembrolizumab 成为增强 OS 的最有效治疗选择（SUCRA 65.03%）。此外，Pembrolizumab 联合化疗可改善 PFS（HR 0.47，95%CI 0.29-0.76）。
我们的分析发现，在 KRAS 基因突变的晚期 NSCLC 患者中，单独使用 Pembrolizumab 作为一线治疗具有更好的疗效。同样，在该患者人群中，单独使用 Nivolumab 作为二线治疗也更为有效。然而，本研究的样本量有限，因此，需要更多的临床数据在后续研究中验证这一发现。
