Comparative Efficacy of Treatments for Brain Metastases from Non-Small Cell Lung Cancer without an EGFR-Mutation/ALK-Rearrangement: A Systematic Review and Network Meta-Analysis

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; Alireza Mansouri

doi:10.1016/j.wneu.2021.10.113

Comparative Efficacy of Treatments for Brain Metastases from Non-Small Cell Lung Cancer without an EGFR-Mutation/ALK-Rearrangement: A Systematic Review and Network Meta-Analysis

World Neurosurg. 2022 Feb:158:e87-e102. doi: 10.1016/j.wneu.2021.10.113. Epub 2021 Oct 21.

Authors

Affiliations

¹ Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
² Division of Neurosurgery, Department of Surgery, Queen's University, Kingston, Ontario, Canada.
³ Division of Neurosurgery, University Health Network, Toronto, Ontario, Canada.
⁴ Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
⁵ Department of Oncology, Queen's University, Kingston, Ontario, Canada.
⁶ Department of Neurosurgery, Penn State Health, Hershey, Pennsylvania, USA; Penn State Cancer Institute, Hershey, Pennsylvania, USA.
⁷ Division of Medical Oncology, National Cancer Center Singapore, Singapore.
⁸ Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA; Department of Hematology/Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA.
⁹ The Preston Robert Tisch Brain Tumor Center, Duke University, Durham, North Carolina, USA.
¹⁰ Department of Neurosurgery, Penn State Health, Hershey, Pennsylvania, USA; Penn State Cancer Institute, Hershey, Pennsylvania, USA. Electronic address: amansouri@pennstatehealth.psu.edu.

PMID: 34688937
DOI: 10.1016/j.wneu.2021.10.113

Abstract

Introduction: As 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.

Methods: We 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.

Results: In 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.

Conclusions: In 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.

Keywords: Brain metastases; Chemotherapy; Immunotherapy; Network meta-analysis; Non–small cell lung cancer.

Publication types

Meta-Analysis
Systematic Review

MeSH terms

Brain Neoplasms* / drug therapy
Brain Neoplasms* / therapy
Carcinoma, Non-Small-Cell Lung* / drug therapy
Carcinoma, Non-Small-Cell Lung* / therapy
ErbB Receptors / genetics
Humans
Immune Checkpoint Inhibitors
Lung Neoplasms* / drug therapy
Lung Neoplasms* / therapy
Mutation / genetics
Network Meta-Analysis
Receptor Protein-Tyrosine Kinases / therapeutic use

Substances

Immune Checkpoint Inhibitors
EGFR protein, human
ErbB Receptors
Receptor Protein-Tyrosine Kinases