Research Paper Advance Articles

Efficacy and safety of therapies for EGFR-mutant non-small cell lung cancer with brain metastasis: an evidence-based Bayesian network pooled study of multivariable survival analyses

Binghao Zhao1, , Yuekun Wang1, , Yaning Wang1, , Wenlin Chen1, , Lizhou Zhou1, , Peng Hao Liu1, , Ziren Kong1, , Congxin Dai1, , Yu Wang1, *, , Wenbin Ma1, *, ,

  • 1 Departments of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
* Equal contribution

Received: February 13, 2020       Accepted: May 27, 2020       Published: July 15, 2020      

https://doi.org/10.18632/aging.103455
How to Cite

Copyright © 2020 Zhao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Preferable treatments for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) with brain metastasis are elusive. The study intended to estimate the relative efficacy and safety of systemic therapies. Clinical trials about therapies for EGFR-mutant, brain-metastatic NSCLC were identified. Progression-free survival (PFS) and overall survival (OS) were analysed using random effects Bayesian network meta-analyses (NMAs) on the hazard ratio (HR)-scale. Nomogram and Kaplan-Meier plots based on clinical or individual factors are displayed using data obtained from the Surveillance Epidemiology and End Results (SEER) database. Third-generation EGFR- tyrosine kinase inhibitors (EGFR-TKI) (osimertinib), EGFR-TKIs + stereotactic radiosurgery (SRS)/whole brain radiotherapy (WBRT) (gefitinib/erlotinib + SRS/WBRT), and EGFR-TKIs (erlotinib) + anti-vascular endothelial growth factor receptor (anti-VEGFR) (bevacizumab) achieved superior PFS (HR: 0.30 (0.15-0.59); HR: 0.47 (0.31-0.72); HR: 0.50 (0.21-1.21) vs. deferring SRS/WBRT) and acceptability; EGFR-TKIs + SRS/WBRT was top ranking (vs. others) for OS followed by third-generation EGFR-TKI. In the dataset cohort of 1173 brain-metastatic NSCLC patients, the 6-month, 1-year, and 3-year survival rates were 59.8%, 41.3%, and 5.6%, respectively. Race and origin, and year of diagnosis were independent predictors of OS. Survival curves showed that the OS of patients varied significantly by histology and race. Third-generation EGFR-TKI and EGFR-TKIs + SRS/WBRT are more effective and potentially acceptable for EGFR-mutant NSCLC with brain metastases balancing OS and PFS. Surgeries without adjuvant therapies cannot significantly improve the OS of brain-metastatic NSCLC patients. The study highlights importance of osimertinib in these patients and provide a reference for clinical treatments.

Abbreviations

EGFR: epidermal growth factor receptor; NSCLC: non-small cell lung cancer; RCT: randomized controlled trials; PFS: progression-free survival; OS: overall survival; NMAs: network meta-analyses; SEER: Surveillance Epidemiology and End Results; EGFR-TKIs: epidermal growth factor receptor tyrosine kinase inhibitors; VEGFR: vascular endothelial growth factor receptor; CNS: central nervous system; SRS: stereotactic radiosurgery; WBRT: whole brain radiotherapy; ORR: objective response rate; RT: radiotherapy; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; ECOG: Eastern Cooperative Oncology Group; ASCO: American Society of Clinical Oncology; ESMO: European Society for Medical Oncology; IASLC: International Association for the Study of Lung Cancer; SNO: the Society for Neuro-oncology; MCMC: Markov Chain Monte Carlo; Crl: credible interval; ICD: International Classification of Disease; AJCC: American Joint Committee on Cancer; C-index: concordance index; DIC: deviance information criteria; HR: hazard ratio; K-M plots: Kaplan-Meier plots; MDT: multiple disciplinary team; GPA: Grade Prognostic Assessment.