Alexander F C Hulsbergen1, Marco Mammi2, Steven H J Nagtegaal3, Asad M Lak4, Vasileios Kavouridis4, Timothy R Smith4, Julian B Iorgulescu5, Rania A Mekary6, Joost J C Verhoeff3, Marike L D Broekman7, John G Phillips8. 1. Department of Neurosurgery, Computational Neuroscience Outcomes Center, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Neurosurgery, Haaglanden Medical Center and Leiden University Medical Center, Leiden University, Leiden, Zuid-Holland, the Netherlands. 2. Department of Neurosurgery, Computational Neuroscience Outcomes Center, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Neuroscience, Neurosurgery Unit, University of Turin, Turin, Italy. 3. Department of Radiation Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. 4. Department of Neurosurgery, Computational Neuroscience Outcomes Center, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts. 5. Department of Neurosurgery, Computational Neuroscience Outcomes Center, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Medical Oncology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts. 6. Department of Pharmaceutical Business and Administrative Sciences, School of Pharmacy, Massachusetts College of Pharmacy and Health Sciences, Boston, Massachusetts. 7. Department of Neurosurgery, Haaglanden Medical Center and Leiden University Medical Center, Leiden University, Leiden, Zuid-Holland, the Netherlands; Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts. 8. Department of Radiation Oncology, Dana Farber Cancer Institute/Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: jphillips@bwh.harvard.edu.
Abstract
PURPOSE: Programmed death receptor ligand 1 (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 AND MATERIALS: In this multi-institutional retrospective cohort study, we identified patients with NSCLC-BM treated with PD-1/PD-L1 inhibitors after local BM treatment (radiation therapy or neurosurgery) but before intracranial progression. Cox proportional hazards models were used to assess the predictive value of PD-L1 expression for overall survival (OS) and intracranial progression-free survival (IC-PFS). RESULTS: Forty-eight patients with BM 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 (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.19-1.02; P = .055). This effect persisted after correcting for lung-graded prognostic assessment and other identified potential confounders (HR, 0.24; 95% CI, 0.10-0.61; P = .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 = .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 = .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-graded prognostic assessment. 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.
PURPOSE: Programmed death receptor ligand 1 (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 AND MATERIALS: In this multi-institutional retrospective cohort study, we identified patients with NSCLC-BM treated with PD-1/PD-L1 inhibitors after local BM treatment (radiation therapy or neurosurgery) but before intracranial progression. Cox proportional hazards models were used to assess the predictive value of PD-L1 expression for overall survival (OS) and intracranial progression-free survival (IC-PFS). RESULTS: Forty-eight patients with BM 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 (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.19-1.02; P = .055). This effect persisted after correcting for lung-graded prognostic assessment and other identified potential confounders (HR, 0.24; 95% CI, 0.10-0.61; P = .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 = .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 = .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-graded prognostic assessment. 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: Luka Brcic; Thomas Klikovits; Zsolt Megyesfalvi; Berta Mosleh; Katharina Sinn; Richard Hritcu; Viktoria Laszlo; Tanja Cufer; Ales Rozman; Izidor Kern; Katja Mohorcic; Marko Jakopovic; Miroslav Samarzija; Sven Seiwerth; Vitezslav Kolek; Ondřej Fischer; Petr Jakubec; Jozef Škarda; Balazs Gieszer; Balazs Hegedus; Janos Fillinger; Ferenc Renyi-Vamos; Anna Buder; Agnes Bilecz; Walter Berger; Michael Grusch; Konrad Hoetzenecker; Walter Klepetko; Mir Alireza Hoda; Martin Filipits; Balazs Dome Journal: Transl Lung Cancer Res Date: 2021-04