Abstract

ObjectiveTo assess the association between PD-L1 expression and driver gene mutations in patients with non-small-cell lung cancer (NSCLC).MethodWe performed a meta-analysis of 26 studies (7541 patients) which were published from 2015 to 2017. Pooled odds ratios (ORs) with 95% confidence intervals (CI) were calculated to describe the correlation. Subgroup analysis was performed based on population characteristics, types of PD-L1 antibodies and quality of individual studies.ResultsA lower frequency of PD-L1 positivity was observed in NSCLCs harboring EGFR mutation (OR: 0.64, 95% CI, 0.45–0.91, p = 0.014). A negative correlation was also found at 1% (OR: 0.35, 95% CI, 0.22–0.55, p = 0.000) and 50% (OR: 0.33, 95% CI, 0.14–0.81, p = 0.015) cutoff for PD-L1 positive, elderly age group (OR: 0.56, 95% CI, 0.35–0.89, p = 0.013), female dominant group (OR: 0.55, 95% CI, 0.29–0.94, p = 0.030) and smoker dominant group (OR: 0.52, 95% CI, 0.29–0.96, p = 0.035). No significant differences in PD-L1 expression were observed among patients with different ALK, BRAF, HER2, PIK3CA status and MET expression level. Higher level of PD-L1 was found in tumors with KRAS mutation (OR: 1.45, 95% CI, 1.18–1.80, p = 0.001). PD-L1 expression level was not significantly different between triple (EGFR/ALK/KRAS) wild type NSCLCs and those with EGFR/ALK/KRAS mutation.ConclusionsPD-L1 expression in EGFR mutated NSCLCs were lower than those in EGFR wild type NSCLCs, while tumors with KRAS mutation showed higher levels of PD-L1.

Highlights

  • Lung cancer is the most common cancer and the leading cause of cancer-related mortality around the world

  • A lower frequency of Programmed cell death 1 ligand 1 (PD-L1) positivity was observed in non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation (OR: 0.64, 95% confidence intervals (CI), 0.45–0.91, p = 0.014)

  • A negative correlation was found at 1% (OR: 0.35, 95% CI, 0.22–0.55, p = 0.000) and 50% (OR: 0.33, 95% CI, 0.14–0.81, p = 0.015) cutoff for PD-L1 positive, elderly age group (OR: 0.56, 95% CI, 0.35–0.89, p = 0.013), female dominant group (OR: 0.55, 95% CI, 0.29–0.94, p = 0.030) and smoker dominant group (OR: 0.52, 95% CI, 0.29–0.96, p = 0.035)

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Summary

Introduction

Lung cancer is the most common cancer and the leading cause of cancer-related mortality around the world. In 2015, a total of 733,300 patients (509,300 men and 224,000 women) were diagnosed with lung cancer in China [1]. About 53% patients of NSCLC are diagnosed at an advanced stage (III b-IV) and, have a poor prognosis [3]. Programmed cell death 1 ligand 1 (PD-L1; referred to as B7-H1), which belongs to B7 family, is an inhibitory cell surface molecule. PD-L1 expressed on NSCLC cells is shown to inhibit T cell proliferation and activation by combining with programmed cell death 1 (PD-1) receptor. Based on the promising results, anti-PD-1 /PD-L1 agents, nivolumab, pembrolizumab and atezolizumab were approved by FDA for treatment of advanced NSCLCs in the past few years [6,7,8,9]

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