Effects of epidermal growth factor receptor-tyrosine kinase inhibitors alone on EGFR-mutant non-small cell lung cancer with brain metastasis

Thorac Cancer. 2016 Nov;7(6):648-654. doi: 10.1111/1759-7714.12379. Epub 2016 Sep 1.

Abstract

Background: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are remarkably effective for treating EGFR-mutant non-small cell lung cancer (NSCLC). However, the individual role of EGFR-TKIs in patients with brain metastasis (BM) arising from EGFR-mutant NSCLC remains unclear.

Methods: Patients with BM secondary to NSCLC and harboring EGFR-activating mutations were retrospectively screened. Patients who received gefitinib or erlotinib to control both extracranial lesions (ECLs) and intracranial lesions (ICLs) were eligible. If ECLs remained stable or remissive while ICLs progressed; asymptomatic BM progressed to symptomatic BM; BM symptoms were not alleviated within two weeks; or BM symptoms deteriorated after initial release, patients received brain radiotherapy or other local treatments and continued taking TKIs until ECLs progression occurred.

Results: In 43 eligible patients, the objective response and disease control rates for ICLs were 57% and 91%, respectively. Median progression-free survival (PFS) was 9.3 months. The median PFS for ICLs and ECLs was 9.7 and 13.7 months, respectively. Non-smokers and second-line TKIs were found to be independent positive prognostic factors for PFS and overall survival (OS) respectively, with a hazard ratio of 0.29 (95% confidence interval [CI] 0.14-0.61; P = 0.001) and 0.34 (95% CI 0.16-0.70; P = 0.003). No significant difference in median OS was observed between patients who did or did not receive brain radiotherapy (23.6 vs. 18.7 months; P = 0.317).

Conclusion: EGFR-TKIs alone are effective for treating BM arising from EGFR-mutant NSCLC. The efficacy of TKIs in ICLs and ECLs should be evaluated separately.

Keywords: Brain metastasis; epidermal growth factor receptor; non-small cell lung cancer; tyrosine kinase inhibitors.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / therapeutic use
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / secondary
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • ErbB Receptors / genetics*
  • Erlotinib Hydrochloride / administration & dosage
  • Erlotinib Hydrochloride / therapeutic use
  • Female
  • Gefitinib
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Male
  • Middle Aged
  • Mutation
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / therapeutic use
  • Quinazolines / administration & dosage
  • Quinazolines / therapeutic use
  • Retrospective Studies
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Quinazolines
  • Erlotinib Hydrochloride
  • EGFR protein, human
  • ErbB Receptors
  • Gefitinib