PD-L1 expression and its effect on clinical outcomes of EGFRmutant NSCLC patients treated with EGFR-TKIs

Objective:Epidermal growth factor receptor(EGFR)activation was reported to upregulate programmed death-ligand 1(PD-L1)expression in lung cancer cells and subsequently contribute to immune escape,indicating its critical role in EGFR-driven lung tumors.This study characterized PD-L1 expression in patients with surgically resected EGFR-mutant non-small cell lung cancer(NSCLC).The effect of PD-L1 expression on clinical outcomes was also investigated in advanced EGFR-mutant NSCLC treated with EGFR-tyrosine kinase inhibitors(TKIs).Methods:In total,73 patients with surgically resected NSCLC and EGFR mutations were identified.PD-L1 expression and CD8+tumor-infiltrating lymphocyte(TIL)density were assessed by immunohistochemistry.A literature review of publications that assessed the predictive and prognostic value of PD-L1 expression in advanced EGFR-mutant NSCLC patients treated with EGFR-TKIs was performed.Results:Nineteen(26.0%)patients were positive for PD-L1 expression,which was significantly associated with concomitant KRAS mutation(P=0.020)and marginally associated with higher CD8+TILs density(P=0.056).Positive PD-L1 expression was associated with markedly inferior overall survival(OS)in multivariate analysis(P=0.032).The combination of PD-L1 and CD8+TILs expression could be used to stratify the population into three groups with distinct prognoses.A meta-analysis of six publications showed that positive PD-L1 expression was not associated with OS[hazard ratio(HR)=0.90;95%confidence interval(CI),0.42–1.38]or progression-free survival(HR=1.03;95 CI,0.73–1.33)in advanced EGFR-mutant NSCLC patients receiving EGFR-TKIs.Conclusions:PD-L1 expression tended to correlate with CD8+TIL expression,concomitant KRAS mutation,and poor survival in surgically resected EGFR-mutant NSCLC.PD-L1 expression was neither the predictive nor the prognostic factor in advanced EGFR-mutant NSCLC patients treated with EGFR-TKIs.