Soluble PD-L1 as a Predictor of the Response to EGFR-TKIs in Non-small Cell Lung Cancer Patients With EGFR Mutations.

Yijun Jia,Chunxia Su,Jiayu Li,Wei Li,Fei Zhou,Xuefei Li,Chao Zhao,Guanghui Gao,Caicun Zhou,Shengxiang Ren

doi:10.3389/fonc.2020.01455

Yijun Jia, Chunxia Su + Show 8 more

Open Access

https://doi.org/10.3389/fonc.2020.01455

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Abstract

Programmed cell death ligand 1 (PD-L1) expressed on tumor tissues is a vital molecule for immune suppression and its impact on the response to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has been reported. The significance of soluble PD-L1 (sPD-L1) for lung cancer patients remains unknown. This study investigated whether sPD-L1 could predict the response of EGFR-mutated non-small cell lung cancer (NSCLC) to EGFR-targeted therapy. We retrospectively evaluated patients who received first-line treatment with EGFR-TKIs for advanced NSCLC with EGFR mutations. Pre-treatment plasma concentrations of PD-L1 and on-treatment (1 month after treatment initiation) plasma concentrations of PD-L1 were measured using the R-plex Human PD-L1 assay. The association between the sPD-L1 level and the clinical outcome was analyzed. Among 66 patients who were eligible for the study, patients with high pre-treatment or on-treatment sPD-L1 levels had decreased objective response rate (ORR) compared with that of patients with low sPD-L1 levels (39.4 vs. 66.7%, p = 0.026 for pre-treatment sPD-L1 level, and 43.5 vs. 73.9%, p = 0.025 for on-treatment sPD-L1 level). A high baseline sPD-L1 level was associated with a shortened progression-free survival (PFS) rate (9.9 vs. 16.1 months, p = 0.005). Both univariate and multivariate analyses showed that a high baseline sPD-L1 level was an independent factor associated with the PFS (hazard ratio [HR] 2.56, p = 0.011). Our study revealed that the sPD-L1 level was strongly related to the outcome of EGFR-TKIs in NSCLC patients harboring EGFR mutations.

Highlights

Lung cancer remains the leading cause of cancer-related death around the world
Patients with a change in soluble progressive disease (PD)-L1 (sPD-L1) level that was lower than the median difference for the entire population were considered to have a reduction in sPD-L1 levels, whereas others were considered to have no reduction in sPD-L1 levels
There were no significant differences in gender, age, histological status, Eastern Cooperative Oncology Group (ECOG) performance status (PS) status, stage, smoking status, EGFR mutation status, type of EGFR-TKI treatment received, metastasis status or T790M mutation at progression between the low sPD-L1 expression group and high sPD-L1 expression group

Summary

INTRODUCTION

Lung cancer remains the leading cause of cancer-related death around the world. Despite significant improvements in the treatment of this malignancy, the prognosis remains poor [1]. In recent decades, targeted therapies such as the EGFR-TKIs have markedly improved the management of NSCLC patients with EGFR mutations [2,3,4]. High levels of PD-L1 expression were reported to be correlated with a primary resistance and predicted a poor response to EGFR-TKIs [13, 14]. These findings may provide implications for using PD-1/PD-L1 inhibitors in patients with EGFR-mutant NSCLC. Our study aimed to investigate the impact of sPD-L1 levels on the treatment response to EGFRTKIs in treatment-naïve NSCLC patients with EGFR mutations

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