• Karanbir Brar, Shervin Taslimi, Yosef Ellenbogen, Jiawen Deng, Winston Hou, Fabio Y Moraes, Michael Glantz, Brad E Zacharia, Aaron Tan, Manmeet S Ahluwalia, Mustafa Khasraw, Gelareh Zadeh, and Alireza Mansouri.
• Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
• World Neurosurg. 2022 Feb 1; 158: e87-e102.

IntroductionAs many as 30% of patients with non-small cell lung cancer (NSCLC) will develop brain metastases (BMs) over the course of their illness. Here, we quantitatively compare the efficacy of the various emerging regimens for NSCLC BMs without a definitive targetable epidermal growth factor receptor mutation/ALK rearrangement.MethodsWe searched MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, CENTRAL, and references of key studies for randomized controlled trials (RCTs) published from inception until June 2020. Comparative RCTs that included ≥10 patients were included. We used a frequentist fixed or random-effects model for network meta-analysis. The outcomes of interest included intracranial progression-free survival (iPFS), overall survival (OS), and overall progression-free survival.ResultsIn total, 18 studies representing 17 trials (n = 2726 patients) were identified. Immune checkpoint inhibitor regimens showed significant improvement in OS compared with chemotherapy alone, including pembrolizumab and chemotherapy (6 studies, hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.21-0.62), atezolizumab alone (HR 0.54, 95% CI 0.33-0.89), and nivolumab and ipilimumab (HR 0.64, 95% CI 0.42-0.97). An improvement in overall PFS was seen with use of pembrolizumab and chemotherapy compared with chemotherapy alone (3 studies, HR 0.42, 95% CI 0.26-0.68). Studies evaluating checkpoint inhibitors did not report iPFS data, and we did not find improvement in iPFS or OS with the addition of any chemotherapy regimen to whole-brain radiation therapy.ConclusionsIn this network meta-analysis, we demonstrate the promising survival benefit with use of checkpoint inhibitor-based regimens in NSCLC BMs without a targetable epidermal growth factor receptor mutation/ALK rearrangement. Moving forward, large-scale BM-focused RCTs are necessary to establish the iPFS benefit of immune checkpoint inhibitor-based immunotherapy in this patient population.Copyright © 2021 Elsevier Inc. All rights reserved.

25 keywords...

hide…