Correlation between PD-L1 high-expression and EGFR variants in non-small cell lung cancer.

Abstract

e21062 Background: In previous studies, researchers have demonstrated that activation of the epidermal growth factor receptor (EGFR)-mutant pathway induced PD-L1 expression. In this study, we explored the correlation between PD-L1 expressions and EGFR variations. Methods: This study enrolled 2417 non-small cell lung cancer(NSCLC) patients harboring diverse EGFR mutations, including exon 19 deletions(19del)(n = 1045), L858R(n = 906), G719X(n = 176), S768I(n = 62), L861Q(n = 89) and exon 20 insertions(20ins)(n = 139). The stages range from I through IV, the majority were female(n = 1452, 60.07%) and adenocarcinoma(n = 1788, 73.98%), median age was 62(range 24-92). In this study, we retrospectively analyzed variants using next-generation sequencing(NGS). PD-L1 status was determined by VENTANA PD-L1 (SP263) Assay, TPS≥50% and TPS＜1% was the cut-off value for PD-L1 high-expression and negative separately. The 95% confidence interval (CI) was used to estimate the precision of the odds ratio (OR). Results: 1) Even though we observed subtle differences of PD-L1 high-expression ratio among various subtypes(19del：9.57%, L858R: 9.27%, G719X: 12.50%, S768I: 11.29%, L861Q: 7.87%, exon 20ins: 12.23%) in total patients, that PD-L1 high-expression was more likely to shown with G719X/S768I/exon 20ins than with 19del/L858R/L861Q, there was no statistically significant between 19del and other mutation：L858R(p = 0.8224), G719X (p = 0.2319), S768I(p = 0.6563), L861Q(p = 0.5982), exon 20ins(P = 0.3247). 2)We analyzed 742 treatment-naive EGFR-mutant NSCLC patients (PD-L1 negative, n = 624; high-expression, n = 118), PD-L1 high-expression group come with higher frequency of EGFR copy number variation(CNV)(OR = 2.2364, 95%CI, 1.4576-3.4312, p = 0.0002). Importantly, the ratio of high-level EGFR CNV(CN≥6) was higher in PD-L1 high-expression group than that in the negative group(OR = 3.0668, 95% CI, 1.3745-6.8427, p = 0.0062). Conclusions: In the newly diagnosed EGFR-mutant NSCLC patients, PD-L1 high-expression patients come with more frequent high-level EGFR CNV. There is no statistical significance between PD-L1 high-expression and EGFR mutation subtypes. As for how the EGFR signal affects PD-L1 expression, the mechanism needs to be further explored. The association between driver genes and immune checkpoints is a definite interest of future investigations.