title: Erlotinib versus radiation therapy for brain metastases in patients with EGFR-mutant lung adenocarcinoma.
abstract: OBJECTIVE
  Radiation therapy (RT) is the principal modality in the treatment of patients with brain metastases (BM). However, given the activity of EGFR tyrosine kinase inhibitors in the central nervous system, it is uncertain whether upfront brain RT is necessary for patients with EGFR-mutant lung adenocarcinoma with BM.
  
  
  METHODS
  Patients with EGFR-mutant lung adenocarcinoma and newly diagnosed BM were identified.
  
  
  RESULTS
  222 patients were identified. Exclusion criteria included prior erlotinib use, presence of a de novo erlotinib resistance mutation, or incomplete data. Of the remaining 110 patients, 63 were treated with erlotinib, 32 with whole brain RT (WBRT), and 15 with stereotactic radiosurgery (SRS). The median overall survival (OS) for the whole cohort was 33 months. There was no significant difference in OS between the WBRT and erlotinib groups (median, 35 vs 26 months; P=.62), whereas patients treated with SRS had a longer OS than did those in the erlotinib group (median, 64 months; P=.004). The median time to intracranial progression was 17 months. There was a longer time to intracranial progression in patients who received WBRT than in those who received erlotinib upfront (median, 24 vs 16 months, P=.04). Patients in the erlotinib or SRS group were more likely to experience intracranial failure as a component of first failure, whereas WBRT patients were more likely to experience failure outside the brain (P=.004).
  
  
  CONCLUSIONS
  The survival of patients with EGFR-mutant adenocarcinoma with BM is notably long, whether they receive upfront erlotinib or brain RT. We observed longer intracranial control with WBRT, even though the WBRT patients had a higher burden of intracranial disease. Despite the equivalent survival between the WBRT and erlotinib group, this study underscores the role of WBRT in producing durable intracranial control in comparison with a targeted biologic agent with known central nervous system activity.
authors.affiliation: Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Naamit K
authors.initials: NK
authors.lastname: Gerber
authors.affiliation: Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Andreas
authors.initials: A
authors.lastname: Rimner
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Weiji
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Riely
authors.affiliation: Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Beal
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Helena A
authors.initials: HA
authors.lastname: Yu
authors.affiliation: Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Chan
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York. Electronic address: wua@mskcc.org.
authors.forename: Abraham J
authors.initials: AJ
authors.lastname: Wu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000556:secondary* / Q000628:therapy*; D001932:Brain Neoplasms / Q000401:mortality / Q000556:secondary* / Q000628:therapy*; D016371:Cranial Irradiation / Q000379:methods / Q000401:mortality; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D016634:Radiosurgery / Q000379:methods / Q000401:mortality; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors