First-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor alone or with whole-brain radiotherapy for brain metastases in patients with EGFR-mutated lung adenocarcinoma

Cancer Sci. 2016 Dec;107(12):1800-1805. doi: 10.1111/cas.13079. Epub 2016 Nov 25.

Abstract

We proposed to compare the outcomes of first-line epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) alone with EGFR-TKI plus whole-brain radiotherapy (WBRT) for the treatment of brain metastases (BM) in patients with EGFR-mutated lung adenocarcinoma. A total of 1665 patients were screened from 2008 to 2014, and 132 were enrolled in our study. Among the 132 patients, 72 (54.5%) harbored a deletion in exon 19, 97 (73.5%) showed multiple intracranial lesions, and 67 (50.8%) had asymptomatic BM. Seventy-nine patients (59.8%) were treated with EGFR-TKI alone, 53 with concomitant WBRT. The intracranial objective response rate was significantly higher in the EGFR-TKI plus WBRT treatment group (67.9%) compared with the EGFR-TKI alone group (39.2%) (P = 0.001). After a median follow-up of 36.2 months, 62.1% of patients were still alive. The median intracranial TTP was 24.7 months (95% CI, 19.5-29.9) in patients who received WBRT, which was significantly longer than in those who received EGFR-TKI alone, with the median intracranial TTP of 18.2 months (95% CI, 12.5-23.9) (P = 0.004). There was no significant difference in overall survival between WBRT and EGFR-TKI alone groups, (median, 48.0 vs 41.1 months; P = 0.740). The overall survival is significantly prolonged in patients who had an intracranial TTP exceeding 22 months compared to those who developed intracranial progression <22 months after treatment, (median, 58.0 vs 28.0 months; P = 0.001). For EGFR-mutated lung adenocarcinoma patients with BM, treatment with concomitant WBRT achieved a higher response rate of BM and significant improvement in intracranial progression-free survival compared with EGFR-TKI alone.

Keywords: Brain metastasis; EGFR mutation; lung adenocarcinoma; prognosis; radiotherapy.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology*
  • Adenocarcinoma of Lung
  • Adult
  • Aged
  • Brain Neoplasms / mortality
  • Brain Neoplasms / secondary*
  • Brain Neoplasms / therapy*
  • Combined Modality Therapy
  • Disease Progression
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics*
  • Female
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Staging
  • Proportional Hazards Models
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Radiotherapy* / methods
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Protein Kinase Inhibitors
  • ErbB Receptors