75. PROGRAMMED DEATH RECEPTOR LIGAND ONE EXPRESSION MAY INDEPENDENTLY PREDICT SURVIVAL IN NON-SMALL CELL LUNG CARCINOMA BRAIN METASTASES PATIENTS RECEIVING IMMUNOTHERAPY

Neuro-Oncology Advances, vol. 2, pp. ii16

Abstract

Abstract BACKGROUND 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. METHODS 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). RESULTS Forty-eight BM patients with available PD-L1 expression were identified. PD-L1 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). CONCLUSIONS In patients with NSCLC-BMs treated with PD-1/PD-L1 checkpoint inhibitors and local treatment, PD-L1 expression may predict OS independent of lung-GPA. 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.

Authors 10

1. Alexander F. C. Hulsbergen Aachen Departments of Neurosurgery

   Brigham and Women's Hospital · Leiden University Medical Center · Medisch Centrum Haaglanden · Stichting Haaglanden Medisch Centrum

   Affiliation as printed

   Computational Neuroscience Outcomes Center, Department of Neurosurgery, Brigham and Women’s Hospital, Boston, MA, USA

   Departments of Neurosurgery, Haaglanden Medical Center and Leiden University Medical Center, The Hague, Netherlands

2. Marco Mammi

   Brigham and Women's Hospital · University of Turin

   Affiliation as printed

   Computational Neuroscience Outcomes Center, Department of Neurosurgery, Brigham and Women’s Hospital, Boston, MA, USA

   Neurosurgery Unit, Department of Neuroscience, University of Turin, Turin, Italy

3. Steven Nagtegaal

   University Medical Center Utrecht

   Affiliation as printed

   Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, Netherlands

4. Vasileios K. Kavouridis

   Brigham and Women's Hospital

   Affiliation as printed

   Computational Neuroscience Outcomes Center, Department of Neurosurgery, Brigham and Women’s Hospital, Boston, MA, USA

5. Timothy Richard Smith

   Brigham and Women's Hospital

   Affiliation as printed

   Computational Neuroscience Outcomes Center, Department of Neurosurgery, Brigham and Women’s Hospital, Boston, MA, USA

6. Bryan Iorgulescu

   Brigham and Women's Hospital

   Affiliation as printed

   Computational Neuroscience Outcomes Center, Department of Neurosurgery, Brigham and Women’s Hospital, Boston, MA, USA

7. Rania A. Mekary

   Brigham and Women's Hospital

   Affiliation as printed

   Computational Neuroscience Outcomes Center, Department of Neurosurgery, Brigham and Women’s Hospital, Boston, MA, USA

8. Joost J.C. Verhoeff

   University Medical Center Utrecht

   Affiliation as printed

   Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, Netherlands

9. Marike L. D. Broekman Aachen Departments of Neurosurgery

   Leiden University Medical Center · Medisch Centrum Haaglanden · Stichting Haaglanden Medisch Centrum

   Affiliation as printed

   Departments of Neurosurgery, Haaglanden Medical Center and Leiden University Medical Center, The Hague, Netherlands

10. John G. Phillips

    Brigham and Women's Hospital

    Affiliation as printed

    Department of Radiation Oncology, Brigham and Women’s Hospital, Boston, MA, USA