title: Brain metastases in patients with ALK+ non-small cell lung cancer: clinical symptoms, treatment patterns and economic burden.
abstract: OBJECTIVE
  Brain metastases (BM) are highly prevalent among anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC) patients; yet little is known about their real-world treatment patterns and clinical and economic burdens. This study aimed to describe these patients' treatment patterns, symptoms, and costs.
  
  
  METHODS
  Retrospective study pooling data from three large administrative databases in the US (08/2011-06/2013). ALK+ NSCLC patients with BM and continuous enrollment for ≥ 60 days before and ≥ 30 days after the first observed BM diagnosis were identified by pharmacy records for crizotinib among patients with lung cancer and BM diagnostic codes.
  
  
  METHODS
  Treatment patterns, symptoms, healthcare resource utilization, and costs, before and after BM diagnosis.
  
  
  RESULTS
  Of the 213 crizotinib patients with BM diagnoses meeting the selection criteria, 23.0% had BM prior to NSCLC diagnosis; 47.4% had BM prior to crizotinib initiation; 19.2% during crizotinib treatment; and 10.3% post-crizotinib treatment. For those diagnosed with BM after NSCLC diagnosis, the median time between the NSCLC and BM diagnoses was 88 days. Following the first observed BM diagnosis, 88.7% used chemotherapy, 63.4% had radiotherapy, and 31.9% had stereotactic radiosurgery. The prevalence of BM-related symptoms substantially increased post-BM-diagnosis: fatigue (from 15% to 39%), headaches (from 5% to 24%), and depression (from 5% to 15%). Monthly costs per patient averaged $5983 before the BM diagnosis and $22,645 after diagnosis. Patients' resource utilization increased significantly post-BM-diagnosis, with a 3-fold increase in OP visits and a 6-fold increase in IP stays. Post-BM-diagnosis costs were driven by pharmacy (42.0%), inpatient (29.6%), and outpatient costs (26.0%).
  
  
  CONCLUSIONS
  The study sample was limited to crizotinib-treated patients.
  
  
  CONCLUSIONS
  Post-BM-diagnosis, patients experience high symptom burden. Post-BM-diagnosis, treatment is highly variable and costly: average monthly costs per patient almost quadrupled post-BM-diagnosis.
authors.affiliation: Analysis Group, Inc. , Montreal, QC , Canada.
authors.forename: Annie
authors.initials: A
authors.lastname: Guérin
authors.forename: Medha
authors.initials: M
authors.lastname: Sasane
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Culver
authors.forename: Katherine
authors.initials: K
authors.lastname: Dea
authors.forename: Roy
authors.initials: R
authors.lastname: Nitulescu
authors.forename: Eric Qiong
authors.initials: EQ
authors.lastname: Wu
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000191:economics / Q000627:therapeutic use; D015415:Biomarkers; D001932:Brain Neoplasms / Q000188:drug therapy / Q000191:economics* / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000191:economics* / Q000473:pathology; D015897:Comorbidity; D000077547:Crizotinib; D003430:Cross-Sectional Studies; D005260:Female; D006295:Health Resources / Q000191:economics* / Q000706:statistics & numerical data; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000191:economics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D011720:Pyrazoles / Q000191:economics* / Q000627:therapeutic use; D011725:Pyridines / Q000191:economics* / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D012189:Retrospective Studies; D014481:United States
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: Brain neoplasms; Costs and cost analysis; Crizotinib; Neoplasm metastasis; Non-small-cell lung cancer; Symptoms