Association between programmed death-ligand 1 expression, immune microenvironments, and clinical outcomes in epidermal growth factor receptor mutant lung adenocarcinoma patients treated with tyrosine kinase inhibitors
Journal
European Journal of Cancer
Journal Volume
124
Pages
110-122
Date Issued
2020
Author(s)
Abstract
Besides being a predictive biomarker of response to immunotherapy in lung cancer in general, programmed death-ligand 1 (PD-L1) is not so well correlated with treatment outcomes of lung adenocarcinoma (ADC) harbouring epidermal growth factor receptor (EGFR) mutations, as reported studies are inconclusive and seldom addressed the issues of response to treatment and resistance. The primary objective is to evaluate the association of PD-L1 and EGFR tyrosine kinase inhibitor (TKI) efficacy, resistance, and relevant clinical outcomes. The secondary objective is to further explore the tumour microenvironments of EGFR mutant tumours with different PD-L1 expression. Using immunohistochemical (IHC) staining, we retrospectively tested PD-L1 expression (Dako 22C3) in the pre-treatment tumours from advanced EGFR mutant lung ADC patients, of whom all were treated with TKIs. Multiplex IHC assay was applied for exploring immune cells in tumour microenvironments. A total of 153 Taiwanese patients were enrolled in our study, of whom a majority of cases were female (58.9%) and non-smokers (75.8%). The objective response rate (ORR) to EGFR TKI and progression-free survival (PFS) were better in patients with PD-L1 expression <50% (ORR/PFS in PD-L1 0% versus 1-49% versus ≥50%: 65.6%/12.5 months versus 56.4%/12.8 months versus 38.9%/5.9 months, P < 0.05). The multivariate analysis showed that PD-L1 <50% was an independent prognostic factor for longer PFS (hazard ratio (HR) 0.433, 95% confidence interval (CI) 0.250-0.751, P = 0.003). Furthermore, tumours with higher PD-L1 expression were less likely to develop a secondary T790M mutation (T790M+ in PD-L1 0% versus 1-49% versus ≥50%: 53.7% versus 35.7% versus 10%, P = 0.024). Multiplex IHC tests were applied in 15 cases and revealed a potential correlation between PD-L1, immune cells, and EGFR TKI responses. Lower pre-treatment PD-L1 is associated with better ORR, PFS, and higher frequency of T790M resistance in EGFR TKI-treated lung ADC patients.
SDGs
Other Subjects
epidermal growth factor receptor; programmed death 1 ligand 1; protein tyrosine kinase inhibitor; CD274 protein, human; EGFR protein, human; epidermal growth factor receptor; programmed death 1 ligand 1; protein kinase inhibitor; adult; aged; Article; cancer prognosis; cancer resistance; cancer survival; clinical outcome; cohort analysis; controlled study; drug efficacy; female; gene mutation; human; immunohistochemistry; lung adenocarcinoma; major clinical study; male; priority journal; progression free survival; protein expression; protein expression level; retrospective study; Taiwanese; tumor microenvironment; biosynthesis; genetics; immunology; lung adenocarcinoma; lung tumor; middle aged; mutation; pathology; tumor microenvironment; very elderly; Adenocarcinoma of Lung; Adult; Aged; Aged, 80 and over; B7-H1 Antigen; ErbB Receptors; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mutation; Progression-Free Survival; Protein Kinase Inhibitors; Retrospective Studies; Tumor Microenvironment
Publisher
Elsevier Ltd
Type
journal article