EGFR TKIs plus WBRT Demonstrated No Survival Benefit Other Than That of TKIs Alone in Patients with NSCLC and EGFR Mutation and Brain Metastases

J Thorac Oncol. 2016 Oct;11(10):1718-28. doi: 10.1016/j.jtho.2016.05.013. Epub 2016 May 26.

Abstract

Introduction: Whether EGFR tyrosine kinase inhibitors (TKIs) plus whole brain radiation therapy (WBRT) provide a better survival benefit than EGFR TKIs alone remains undetermined in patients with NSCLC with EGFR mutation and brain metastases (BMs).

Methods: A total of 230 patients with NSCLC with EGFR mutation and BM were identified. Within this group, 116 patients received EGFR TKIs alone (as first-line therapy in 91 cases) and 51 patients received EGFR TKIs plus WBRT therapy (as first-line treatment in 30 cases).

Results: Compared with TKIs alone, EGFR TKIs plus WBRT had no superior intracranial progression-free survival (PFS) (6.9 versus 7.4 months [p = 0.232]) and systemic PFS (7.5 versus 7.9 months [p = 0.546]) but were associated with worse overall survival (OS) (21.6 versus 26.4 months [p = 0.049]) in NSCLC with EGFR mutation and BM. Chemotherapy plus WBRT was shown to have an intracranial PFS (5.2 versus 5.9 months [p = 0.339]) and OS (10.5 versus 11.0 months [p = 0.977]) similar to those with chemotherapy alone in patients with EGFR of unknown or wild-type status. In multivariate analysis, EGFR mutation was found to be an independent risk factor for BM (hazard ratio = 1.476, p = 0.039) and also a significant independent prognostic factor for OS in patients with NSCLC with BM (hazard ratio = 0.601, p = 0.028).

Conclusions: The addition of WBRT to EGFR TKIs did not appear to have survival benefit superior to that of EGFR TKIs alone in with EGFR-mutant NSCLC with BM. WBRT also did not bring additional benefit to chemotherapy in patients with BM and EGFR of wild-type or unknown status.

Keywords: Brain metastasis; Epidermal growth factor receptor mutations; Non–small cell lung cancer; Tyrosine kinase inhibitors; Whole brain radiation therapy.

MeSH terms

  • Aged
  • Brain Neoplasms / mortality
  • Brain Neoplasms / secondary*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cohort Studies
  • ErbB Receptors / genetics*
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Protein Kinase Inhibitors / therapeutic use*
  • Retrospective Studies
  • Survival Analysis

Substances

  • Protein Kinase Inhibitors
  • ErbB Receptors