Research Paper Volume 12, Issue 14 pp 14244—14270
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
- 1 Departments of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Received: February 13, 2020 Accepted: May 27, 2020 Published: July 15, 2020
https://doi.org/10.18632/aging.103455How to Cite
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.