Association Between EGFR Mutation Status and Immune Checkpoint Inhibitors and PD-L1 Expression in Non-Small-Cell Lung Cancer: A Meta-Analysis

Background: A systematic search was performed on the Web of Science, PubMed, Embase, and Cochrane databases. The meta-analysis was performed to evaluate the effect of epidermal growth factor receptor (EGFR) mutation status on programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) immune checkpoint inhibitors, and the association between EGFR mutation status and PD-L1 expression in non-small cell lung cancer (NSCLC) patients. Methods: Pooled effect (HR/OR) with 95% CI was calculated, the source of heterogeneity was explored by subgroup analysis and meta-regression using Stata/SE 15.0. Meta-analysis of the association between EGFR mutation status and overall survival in NSCLC with immunotherapy was calculated from four randomized controlled trials.  Results: We found that immune checkpoint inhibitors significantly prolonged overall survival (OS) over docetaxel overall (HR: 0.71, 95% CI: 0.64-0.79) and in the EGFR wild-type (HR=0.67, 95% CI=0.60-0.75), but not in the EGFR-mutant subgroup (HR=1.11, 95% CI=0.80-1.52). Meta-analysis of the association between EGFR mutation status and PD-L1 expression in NSCLC included 32 studies. The pooled OR and 95% CI were 0.60 (0.46 0.80), calculated by random effects model. No source of heterogeneity was found in subgroup analysis. The sensitivity analysis was carried out with a fixed model, and the influence of a single study on the pooled results showed no significant change with robust meta-analysis methods. Harbord s weighted linear regression test (P=0.956) and Peters regression test (P=0.489) indicated no significant publication bias. Conclusions: The benefit of PD-1/PD-L1 immune checkpoint inhibitor treatment in patients with EGFR-mutated NSCLC is not obvious and may due to the lower expression of PD-L1. Funding: This study was supported by Fujian Program for Outstanding Young Researchers in University awarded by Education Department of Fujian (Grant Number 2017B019), Fujian Provincial Health Research Talents Training Programme Medical Innovation Project (Grant Number 2019- CX-33), Joint Funds for the innovation of science and Technology，Fujian province (Grant Number 2019Y9022), and Fujian Provincial Health Research Talents Training Programme Youth Research Project (Grant Number 2019-1- 58).The funding sponsors played no role in study design, data collection, data analysis, interpretation, writing of the report, and the decision to submit the paper for publication. Declaration of Interest: None to declare. Ethical Approval: This study was approved by the Institutional Review Board of Fujian Medical University (Fuzhou, China).