Ching-Yao Yang1, Wei-Yu Liao1, Chao-Chi Ho1, Kuan-Yu Chen1, Tzu-Hsiu Tsai1, Chia-Lin Hsu1, Kang-Yi Su2, Yih-Leong Chang3, Chen-Tu Wu4, Chia-Chi Hsu5, Bin-Chi Liao6, Wei-Hsun Hsu6, Jih-Hsiang Lee6, Chia-Chi Lin6, Jin-Yuan Shih7, James C-H Yang6, Chong-Jen Yu1. 1. Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei City, Taiwan. 2. Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei City, Taiwan. 3. Department of Pathology, National Taiwan University Hospital, National Taiwan University Cancer Center and National Taiwan University College of Medicine, Taipei City, Taiwan. Electronic address: ntuhylc@gmail.com. 4. Department of Pathology, National Taiwan University Hospital, National Taiwan University Cancer Center and National Taiwan University College of Medicine, Taipei City, Taiwan. Electronic address: ipohdamu@gmail.com. 5. Department of Oncology, National Taiwan University Hospital, Taipei City, Taiwan; Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan. 6. Department of Oncology, National Taiwan University Hospital, Taipei City, Taiwan. 7. Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei City, Taiwan. Electronic address: jyshih@ntu.edu.tw.
Abstract
INTRODUCTION: 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. METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSIONS: Lower pre-treatment PD-L1 is associated with better ORR, PFS, and higher frequency of T790M resistance in EGFR TKI-treated lung ADC patients.
INTRODUCTION: 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. METHODS AND MATERIALS: Using immunohistochemical (IHC) staining, we retrospectively tested PD-L1 expression (Dako 22C3) in the pre-treatment tumours from advanced EGFR mutant lung ADCpatients, of whom all were treated with TKIs. Multiplex IHC assay was applied for exploring immune cells in tumour microenvironments. RESULTS: 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. CONCLUSIONS: Lower pre-treatment PD-L1 is associated with better ORR, PFS, and higher frequency of T790M resistance in EGFR TKI-treated lung ADCpatients.