PD-L1 Expression and Outcome in Patients with Metastatic Non-Small Cell Lung Cancer and EGFR Mutations Receiving EGFR-TKI as Frontline Treatment

Abstract

Cheng-Yu Chang,1,* Yi-Chun Lai,2,3,* Yu-Feng Wei,4,5,* Chung-Yu Chen,6,7,* Shih-Chieh Chang2,8 1Division of Chest Medicine, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan; 2Division of Chest Medicine, Department of Internal Medicine, National Yang Ming Chiao Tung University Hospital, Yi-Lan, Taiwan; 3Faculty of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 4School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, Taiwan; 5Department of Internal Medicine, E-Da Cancer Hospital, Kaohsiung, Taiwan; 6Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin County, Taiwan; 7College of Medicine, National Taiwan University, Taipei, Taiwan; 8Department of Critical Care Medicine, National Yang Ming Chiao Tung University Hospital, Yi-Lan, Taiwan*These authors contributed equally to this workCorrespondence: Shih-Chieh ChangDivision of Chest Medicine, Department of Internal Medicine, National Yang Ming Chiao Tung University Hospital, No. 169, Siaoshe Road, Yi-Lan, 260, TaiwanTel [phone]Fax [phone]Email [email protected]: Epidermal growth factor receptor (EGFR) mutations are most common in Eastern Asia, and frequencies of 30– 50% have been reported. EGFR-tyrosine kinase inhibitors (TKIs) are recommended as first-line therapeutic options for non-small cell lung cancer (NSCLC) with sensitizing EGFR mutations. Several immune checkpoint inhibitors have been successful in improving the outcomes of advanced lung cancer. The expression of programmed cell death-ligand 1 (PD-L1) on tumor cells plays an important role in predicting the efficacy of programmed cell death protein 1/PD-L1 inhibitors. The role of PD-L1 expression in tumors with EGFR mutation and its influence on clinical outcomes remain controversial.Methods: Patients with newly diagnosed metastatic NSCLC with sensitizing EGFR mutations who received the standard treatment, ie, EGFR-TKIs for mutant adenocarcinoma as the first-line treatment, were enrolled in this retrospective study. EGFR mutations and PD-L1 expression levels were detected by Cobas RT-PCR and Dako 22C3 immunohistochemistry staining, respectively.Results: From January 2011 to February 2019, 114 patients were enrolled. The average age was 62 years (range 34– 92), and 45 (39.5%) patients were male. Among these patients, EGFR mutation analysis revealed exon 19 in-frame deletion in 55 (48.2%) patients, exon 21 L858R in 53 (46.5%) patients, and uncommon mutations in 6 (5.3%) patients. Among these patients with EGFR mutations, PD-L1 expression levels by tumor proportion score (TPS) were < 1% in 54 (46.9%) patients, 1– 49% in 50 (44.2%) patients, and ≥ 50% in 10 (8.8%) patients. All patients received EGFR-TKIs as first-line treatment, and in the Kaplan-Meier analysis, progression-free survival was not significantly different among groups with different PD-L1 expression status.Conclusion: For patients with metastatic NSCLC and EGFR mutations, PD-L1 expression is not uncommon, but no significant influence on clinical outcomes was observed in patients receiving standard initial treatment.Keywords: programmed death-ligand 1, epidermal growth factor receptor mutation, epidermal growth factor receptor tyrosine kinase inhibitors

Keywords

• programmed death-ligand 1
• epidermal growth factor receptor mutation
• epidermal growth factor receptor tyrosine kinase inhibitors