Kuo-Hsuan Hsu1, Yen-Hsiang Huang2, Jeng-Sen Tseng3, Kun-Chieh Chen4, Wen-Hui Ku5, Kang-Yi Su6, Jeremy J W Chen7, Huei-Wen Chen8, Sung-Liang Yu9, Tsung-Ying Yang10, Gee-Chen Chang11. 1. Division of Critical Care and Respiratory Therapy, Department of Internal Medicine, Taichung Veterans General Hospital, No. 1650, Sect. 4, Taiwan Boulevard, Taichung, 407, Taiwan; Institute of Biomedical Sciences, National Chung Hsing University, No. 145, Xingda Rd., South Dist., Taichung, 402, Taiwan. Electronic address: vghryan@gmail.com. 2. Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, No. 1650, Sect. 4, Taiwan Boulevard, Taichung, 407, Taiwan. Electronic address: waynehuang0622@gmail.com. 3. Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, No. 1650, Sect. 4, Taiwan Boulevard, Taichung, 407, Taiwan; Faculty of Medicine, School of Medicine, National Yang-Ming University, No. 155, Sect. 2, Linong St., Taipei, 112, Taiwan. Electronic address: tzeng64@gmail.com. 4. Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, No. 1650, Sect. 4, Taiwan Boulevard, Taichung, 407, Taiwan. Electronic address: ckjohn@mail2000.com.tw. 5. Department of Clinical Pathology, Taipei Institute of Pathology, Taiwan. Electronic address: whku0322@gmail.com. 6. Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, No. 1, Sect. 1, Jen Ai Road, Taipei, 100, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, No. 7, Zhung-Shan South Road, Taipei, 100, Taiwan. Electronic address: jwchen@dragon.nchu.edu.tw. 7. Institute of Biomedical Sciences, National Chung Hsing University, No. 145, Xingda Rd., South Dist., Taichung, 402, Taiwan. Electronic address: jwchen@dragon.nchu.edu.tw. 8. Graduate Institute of Toxicology, National Taiwan University, No. 1, Sect. 1, Jen-Ai Rd., Taipei, 100, Taiwan. Electronic address: shwchen@ntu.edu.tw. 9. Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, No. 1, Sect. 1, Jen Ai Road, Taipei, 100, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, No. 7, Zhung-Shan South Road, Taipei, 100, Taiwan; Center of Genomic Medicine, National Taiwan University College of Medicine, No. 2, Syu-jhou Road, Taipei, 100, Taiwan; Department of Pathology and Graduate Institute of Pathology, College of Medicine, National Taiwan University, No. 7., Chung San South Road, Taipei, 100, Taiwan; Center for Optoelectronic Biomedicine, College of Medicine, National Taiwan University, No. 1, Sect. 1, Jen Ai Road, Taipei, 100, Taiwan. Electronic address: slyu@ntu.edu.tw. 10. Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, No. 1650, Sect. 4, Taiwan Boulevard, Taichung, 407, Taiwan; Faculty of Medicine, School of Medicine, National Yang-Ming University, No. 155, Sect. 2, Linong St., Taipei, 112, Taiwan. Electronic address: jonyin@gmail.com. 11. Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, No. 1650, Sect. 4, Taiwan Boulevard, Taichung, 407, Taiwan; Faculty of Medicine, School of Medicine, National Yang-Ming University, No. 155, Sect. 2, Linong St., Taipei, 112, Taiwan; Comprehensive Cancer Center, Taichung Veterans General Hospital, No. 1650, Sect. 4, Taiwan Boulevard, Taichung, 407, Taiwan. Electronic address: august@vghtc.gov.tw.
Abstract
OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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%. CONCLUSIONS: 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.
OBJECTIVES: 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 adenocarcinomapatients. MATERIALS AND METHODS: From 2012-2017, we enrolled advanced EGFR-mutant lung adenocarcinomapatients 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. RESULTS: 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%. CONCLUSIONS: Treatment for advanced EGFR-mutant lung adenocarcinomapatients displaying a higher PD-L1 expression level experienced a higher frequency of primary resistance to EGFR-TKIs.