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EGFR mutation status in non-small cell lung cancer receiving PD-1/PD-L1 inhibitors and its correlation with PD-L1 expression: a meta-analysis

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Abstract

Meta-analysis was performed on the Web of Science, PubMed, Embase, and Cochrane databases 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. Pooled effect (hazard ratio/odds ratio, HR/OR) with 95% confidence interval (CI) was calculated, and 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 (OS) in NSCLC with immunotherapy was calculated from four randomized controlled trials. We found that immune checkpoint inhibitors significantly prolonged 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. 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. The limited benefit of single-agent PD-1/PD-L1 inhibitors in the second-line or later setting for EGFR-mutated NSCLC may be partly due to the lower expression of PD-L1.

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Abbreviations

ALK:

Anaplastic lymphoma kinase

ECOG:

Eastern cooperative oncology group

EGFR:

Epidermal growth factor receptor

ERK:

Extracellular signal-regulated kinase

MAPK:

Mitogen-activated protein kinase

MEK:

Mitogen/extracellular signal-regulated kinases

NF-κB:

Nuclear factor kappa-B

NSCLC:

Non-small cell lung cancer

p–c-Jun:

Phospho-c-Jun

PD-1:

Programmed cell death protein 1

PD-L1:

Programmed death ligand 1

p-ERK:

Phospho-extracellular regulated protein kinases

PS:

Performance status

PI3K-AKT:

Phosphatidylinositide 3-kinases-protein kinase B

SCLC:

Small cell lung cancer

STAT:

Signal transducer and activator of transcription

STROBE-ME:

The strengthening of reporting observational studies in epidemiology-molecular epidemiology

TKIs:

Tyrosine kinase inhibitors

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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, or the decision to submit the paper for publication.

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  1. Huimin Yang and Jinxiu Zhu have been contributed equally to this paper.

Authors and Affiliations

  1. Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, 350108, China

    Huimin Yang, Yuhang Liu, Lin Cai & Fei He

  2. Fujian Provincial Key Laboratory of Environment Factors and Cancer, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350108, China

    Huimin Yang, Yuhang Liu, Lin Cai & Fei He

  3. Department of Oncology, Fuzhou Pulmonary Hospital of Fujian, Fuzhou, 350001, China

    Jinxiu Zhu

  4. Department of Thoracic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350001, China

    Rendong Xiao & Minglian Qiu

  5. Experiment Center, School of Public Health, Fujian Medical University, Fuzhou, 350122, China

    Fanglin Yu

  6. Fujian Digital Institute of Tumor Big Data, Fujian Medical University, Fuzhou, 350122, China

    Fei He

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Contributions

HF and QML made substantial contributions to the conception and design of the study. YHM and ZJX contributed to data acquisition, and data analysis and interpretation. YHM, XRD, LYH, and ZJX wrote the manuscript. YFL and CL proofread the manuscript. All authors agree to be accountable for all aspects of the work. All authors have read and approved the final manuscript.

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Correspondence to Minglian Qiu or Fei He.

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Yang, H., Zhu, J., Xiao, R. et al. EGFR mutation status in non-small cell lung cancer receiving PD-1/PD-L1 inhibitors and its correlation with PD-L1 expression: a meta-analysis. Cancer Immunol Immunother 71, 1001–1016 (2022). https://doi.org/10.1007/s00262-021-03030-2

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