PD-L1 expression and its effect on clinical outcomes of EGFR-mutant NSCLC patients treated with EGFR-TKIs

• Main Authors: Yuchen Bai, Xiaoxia Chen, Likun Hou, Jun Qian, Tao Jiang, Caicun Zhou, Maciej Ciebiada
• Format: Article
• Language: English
• Published: China Anti-Cancer Association 2018-12-01
• Series: Cancer Biology & Medicine
• Subjects: Non-small cell lung cancer; EGFR mutation; PD-L1; CD8; survival
• Online Access: http://www.cancerbiomed.org/index.php/cocr/article/view/1294
• ISSN: 2095-3941; 2095-3941

<b>Objective: </b> Epidermal growth factor receptor (EGFR) activation was reported to upregulate programmed death-ligand 1 (PD-L1) expression in lung cancer cells and subsequently contribute to immune escape, indicating its critical role in EGFR-driven lung tumors. This study characterized PD-L1 expression in patients with surgically resected EGFR-mutant non-small cell lung cancer (NSCLC). The effect of PD-L1 expression on clinical outcomes was also investigated in advanced EGFR-mutant NSCLC treated with EGFR-tyrosine kinase inhibitors (TKIs).<b>Methods: </b> In total, 73 patients with surgically resected NSCLC and EGFR mutations were identified. PD-L1 expression and CD8+ tumor-infiltrating lymphocyte (TIL) density were assessed by immunohistochemistry. A literature review of publications that assessed the predictive and prognostic value of PD-L1 expression in advanced EGFR-mutant NSCLC patients treated with EGFR-TKIs was performed.<b>Results: </b> Nineteen (26.0%) patients were positive for PD-L1 expression, which was significantly associated with concomitant KRAS mutation (<i>P</i> = 0.020) and marginally associated with higher CD8+ TILs density (<i>P</i> = 0.056). Positive PD-L1 expression was associated with markedly inferior overall survival (OS) in multivariate analysis (<i>P</i> = 0.032). The combination of PD-L1 and CD8+ TILs expression could be used to stratify the population into three groups with distinct prognoses. A meta-analysis of six publications showed that positive PD-L1 expression was not associated with OS [hazard ratio (HR) = 0.90; 95% confidence interval (CI), 0.42–1.38] or progression-free survival (HR = 1.03; 95 CI, 0.73–1.33) in advanced EGFR-mutant NSCLC patients receiving EGFR-TKIs.<b>Conclusions: </b> PD-L1 expression tended to correlate with CD8+ TIL expression, concomitant KRAS mutation, and poor survival in surgically resected EGFR-mutant NSCLC. PD-L1 expression was neither the predictive nor the prognostic factor in advanced EGFR-mutant NSCLC patients treated with EGFR-TKIs.