Significance of Programmed Death Receptor Ligand One Expression in Brain Metastases of Non-Small Cell Lung Carcinoma

Purpose/Objective(s) Survival in patients with metastatic non-small cell lung carcinoma (NSCLC) has considerably increased in recent years, in part due to the advent of programmed death/programmed death ligand one (PD-1/PD-L1) inhibitors. There is increasing evidence that patients with NSCLC brain metastases (BMs) also benefit from these novel therapies. PD-L1 expression as assessed by immunohistochemistry is known to predict response to PD-L1/PD-1 checkpoint inhibitors. However, it is not known whether this biomarker has prognostic significance in patients with BMs. Therefore, the aim of this study was to assess whether PD-L1 expression predicts survival in patients with NSCLC BMs treated with radiotherapy or neurosurgery as well as PD-1/PD-L1 inhibitors, after adjusting for the lung-Graded Prognostic Assessment (lung-GPA). Materials/Methods This was a multi-institutional retrospective study. Patient records from three hospitals were reviewed to identify NSCLC BM patients who were treated with PD-1/PD-L1 inhibitors after intracranial treatment (resection, SRS (stereotactic radiosurgery/radiotherapy (SRS/SRT)), or whole-brain radiotherapy) but before intracranial progression. PD-L1 expression was considered positive in case of >1% histopathological staining. Cox proportional hazards model was used to assess prognostic significance of PD-L1 expression. Results Forty-eight patients with available PD-L1 expression were identified; median follow-up in this cohort was 24.7 months. Intracranial treatment consisted of SRS (n = 37), SRT (n = 3), resection (n = 7), or WBRT (n = 1). Intracranial treatment for newly diagnosed BMs was given to 30 patients; while 18 were treated for a recurrent BM. PD-L1 expression was positive in 33 patients (69%). In this cohort, median survival was 21.7 months. When split by lung-GPA, median survival in months was as follows: GPA 0-1: 11.4 (n = 6), GPA 1.5 – 2: 16.3 (n = 22), GPA 2.5 – 3: median not reached (n = 17); GPA 3.5 – 4: 14.6 (n = 3). In univariate analysis, PD-L1 expression was a borderline significant predictor for overall survival (HR = 0.44; 95% CI 0.19 – 1.00; p = 0.05). In multivariate analysis, PD-L1 was prognostic for overall survival (HR = 0.36, 95% CI = 0.14 – 0.90; p = 0.03) after correcting for lung-GPA, type of intracranial treatment, and newly diagnosed vs recurrent BMs. Conclusion PD-L1 expression may be a prognostic factor independent of lung-GPA in patients with NSCLC BMs who underwent treatment with PD-1/PD-L1 checkpoint inhibitors. Larger studies are required to validate this finding.