Efficacy of immune checkpoint inhibitors in advanced non‐small cell lung cancer patients with KRAS mutations: A network meta‐analysis

Abstract

Abstract Objective 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. Method 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). Result 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). Conclusion 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.

Keywords

• immune checkpoint inhibitors
• KRAS mutation
• network meta‐analysis
• non‐small cell lung cancer
• programmed cell death ligand‐1
• programmed cell death‐1