title: Cost-effectiveness of multiplexed predictive biomarker screening in non-small-cell lung cancer.
abstract: BACKGROUND
  Population-wide screening for epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements to inform cancer therapy in non-small-cell lung cancer (NSCLC) is recommended by guidelines. We estimated cost-effectiveness of multiplexed predictive biomarker screening in metastatic NSCLC from a societal perspective in the United States.
  
  
  METHODS
  We constructed a microsimulation model to compare the life expectancy and costs of multiplexed testing and molecularly guided therapy versus treatment with cisplatin-pemetrexed (CisPem). All testing interventions included a two-step algorithm of concurrent EGFR mutation and ALK overexpression testing with immunohistochemistry followed by ALK rearrangement confirmation with a fluorescence in situ hybridization assay for immunohistochemistry-positive results. Three strategies were included: "Test-treat" approach, where molecularly guided therapy was initiated after obtainment of test results; "Empiric switch therapy," with concurrent initiation of CisPem and testing and immediate switch to test-result conditional treatment after one cycle of CisPem; and "Empiric therapy" approach in which CisPem was continued for four cycles before start of a tyrosine kinase inhibitor.
  
  
  RESULTS
  The incremental cost-effectiveness ratio for "Test-treat" compared with treatment with CisPem was $136,000 per quality-adjusted life year gained. Both empiric treatment approaches had less favorable incremental cost-effectiveness ratios. "Test-treat" and "Empiric switch therapy" yielded higher expected outcomes in terms of quality-adjusted life years and life-years than "Empiric therapy." These results were robust across plausible ranges of model inputs.
  
  
  CONCLUSIONS
  From a societal perspective, our cost-effectiveness results support the value of multiplexed genetic screening and molecularly guided therapy in metastatic NSCLC.
authors.affiliation: *Institute for Technology Assessment, Massachusetts General Hospital, Harvard University, Boston, Massachusetts; †Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts; ‡Department of Economics, Harvard University, Cambridge, Massachusetts; §Department of Health Care Policy, Harvard Medical School, Boston, Massachusetts; ‖Department of Pathology, Brigham and Women' Hospital, Harvard Medical School, Boston, Massachusetts; and ¶Institute for Technology Assessment, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Romanus
authors.forename: Stephanie
authors.initials: S
authors.lastname: Cardarella
authors.forename: David
authors.initials: D
authors.lastname: Cutler
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Landrum
authors.forename: Neal I
authors.initials: NI
authors.lastname: Lindeman
authors.forename: G Scott
authors.initials: GS
authors.lastname: Gazelle
mesh_terms: D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000191:economics / Q000235:genetics*; D003362:Cost-Benefit Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D055088:Early Detection of Cancer / Q000191:economics* / Q000379:methods; D005260:Female; D015321:Gene Rearrangement; D005820:Genetic Testing / Q000191:economics* / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000175:diagnosis / Q000191:economics / Q000235:genetics*; D008297:Male; D009154:Mutation; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D004273:DNA, Neoplasm; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases