Programmed Death Receptor Ligand One Expression May Independently Predict Survival In Non-Small Cell Lung Carcinoma Brain Metastases Patients Receiving Immunotherapy

Abstract

Programmed death receptor ligand one (PD-L1) expression is known to predict response to PD-1/PD-L1 inhibitors in non-small cell lung cancer (NSCLC). However, the predictive role of this biomarker in brain metastases (BMs) is unknown. The aim of this study was to assess whether PD-L1 expression predicts survival in patients with NSCLC BMs treated with PD-1/PD-L1 inhibitors, after adjusting for established prognostic models. In this multi-institutional retrospective cohort study, we identified NSCLC-BM patients treated with PD-1/PD-L1 inhibitors after local BM treatment (radiotherapy or neurosurgery) but before intracranial progression. Cox proportional hazards models were used to assess predictive value PD-L1 expression for overall survival (OS) and intracranial progression free survival (IC-PFS). Forty-eight BM patients with available PD-L1 expression were identified. PDL1 expression was positive in 33 patients (69%). Median survival was 26 months. In univariable analysis, PD-L1 predicted favorable OS (HR = 0.44; 95% CI 0.19 – 1.02; p = 0.055). This effect persisted after correcting for lung-graded prognostic assessment (lung-GPA) and other identified potential confounders (HR = 0.24; 95% CI = 0.10 – 0.61; p = 0.002). Moreover, when modeled as a continuous variable, there appeared to be a proportional relationship between percentage of PD-L1 expression and survival (HR = 0.86 per 10% expression, 95% CI 0.77 – 0.98, p = 0.02). In contrast, PD-L1 expression did not predict IC-PFS in uni- or multivariable analysis (adjusted HR = 0.54, 95% CI 0.26 – 1.14, p = 0.11). In patients with NSCLC-BMs treated with PD-1/PD-L1 checkpoint inhibitors and local treatment, PD-L1 expression may predict OS independent of lungGPA. IC-PFS did not show association with PD-L1 expression, although the present analysis may lack power to assess this. Larger studies are required to validate these findings.