High PD-L1 expression correlates with primary resistance to EGFR-TKIs in treatment naïve advanced EGFR-mutant lung adenocarcinoma patients

• Published in: Lung cancer (Amsterdam, Netherlands) Vol. 127; pp. 37 - 43
• Main Authors: Hsu, Kuo-Hsuan, Huang, Yen-Hsiang, Tseng, Jeng-Sen, Chen, Kun-Chieh, Ku, Wen-Hui, Su, Kang-Yi, Chen, Jeremy J.W., Chen, Huei-Wen, Yu, Sung-Liang, Yang, Tsung-Ying, Chang, Gee-Chen
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.01.2019
• Subjects: Adenocarcinoma; Adenocarcinoma of Lung - drug therapy; Adenocarcinoma of Lung - genetics; Aged; Antineoplastic Agents - therapeutic use; Drug Resistance, Neoplasm; Epidermal growth factor receptor mutation; ErbB Receptors - antagonists & inhibitors; ErbB Receptors - genetics; Female; Gene Expression Regulation, Neoplastic; Humans; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Male; Mutation - genetics; Neoplasm Staging; Primary resistance; Programmed Cell Death 1 Receptor - genetics; Programmed Cell Death 1 Receptor - metabolism; Programmed cell death-ligand 1; Protein Kinase Inhibitors - therapeutic use; Retrospective Studies; Adenocarcinoma; Epidermal growth factor receptor mutation; Primary resistance; Lung cancer; Programmed cell death-ligand 1
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2018.11.021

•The level of PD-L1 expression can predict efficacy of EGFR-TKI.•Higher PD-L1 expression had high incidence of primary resistance to EGFR TKI.•Higher PD-L1 expression had shorter progression-free survival. The main objective was to investigate the relationship between Programmed cell Death-ligand 1 (PD-L1) expression levels and the frequency of primary resistance to Epidermal Growth Factor Receptor (EGFR)-Tyrosine Kinase Inhibitor (TKI) in treatment naïve advanced EGFR-mutant lung adenocarcinoma patients. From 2012–2017, we enrolled advanced EGFR-mutant lung adenocarcinoma patients who displayed primary resistance to EGFR-TKI therapy, along with patients with disease control, and patients experiencing either stable disease or partial response to EGFR-TKI treatment. Sixty-six patients were enrolled as the primary resistance group, while 57 patients were included as the disease control group. Fifteen-five (22.7%) patients had a PD-L1 Tumor Proportion Score (TPS) ≧50% in the primary resistance group, with only one patient (1.8%) having that score in the disease control group (P＜0.001). Twenty (30.3%) patients had a PD-L1 ≧25% in the primary resistance group, with 2 (3.5%) patients having that level in the disease control group (P＜0.001). Thirty (45.5%) patients had a PD-L1 ≧1% in the primary resistance group, with 7 (12.3%) patients at that level in the disease control group (P = 0.001). Patients with a PD-L1≧1% displayed a higher incidence of primary resistance to EGFR-TKIs than those with a PD-L1＜1% (Odds Ratio (OR), 5.95; 95% Confidence Interval (CI), 2.35–15.05; P＜0.001). The phenomenon existed still when the cutoff value was changed to both 25% (OR, 11.96; 95% CI, 2.65–53.87; P = 0.001) and 50% (OR, 16.47; 95% CI, 2.10–129.16; P = 0.008). The estimated median Progression-free Survival (PFS) rate was 7.3 months in patients with a PD-L1＜1%, 2.1 months in patients with a PD-L1≧1%, 1.8 months in patients with a PD-L1≧25%, and 1.6 months in patients with a PD-L1≧50%. Treatment for advanced EGFR-mutant lung adenocarcinoma patients displaying a higher PD-L1 expression level experienced a higher frequency of primary resistance to EGFR-TKIs.