title: Cost-Effectiveness and Value of Information of Erlotinib, Afatinib, and Cisplatin-Pemetrexed for First-Line Treatment of Advanced EGFR Mutation-Positive Non-Small-Cell Lung Cancer in the United States.
abstract: OBJECTIVE
  To determine the cost-effectiveness of tyrosine kinase inhibitors erlotinib or afatinib, or chemotherapy cisplatin-pemetrexed, for first-line treatment of advanced epithelial growth factor receptor mutation-positive non-small-cell lung cancer in the United States. We also assessed the expected benefit of further research to reduce uncertainty regarding which treatment is optimal.
  
  
  METHODS
  We developed a Markov model to compare the cost-effectiveness of erlotinib, afatinib, and cisplatin-pemetrexed. Model transition and adverse-effect probabilities were from two published phase III trials: EURTAC (Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer) and LUX-Lung (Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma) 3. EURTAC survival estimates were corrected for patients entering the trial with more severe disease, compared with LUX-Lung 3. Health utilities and costs were from national estimates or the published literature. Inputs were modeled as distributions for probabilistic sensitivity analysis and expected value of perfect information (EVPI) analysis to estimate the expected benefit of reducing uncertainty regarding the decision of optimal treatment.
  
  
  RESULTS
  In the base case, both tyrosine kinase inhibitors were more cost-effective than cisplatin-pemetrexed. Erlotinib had an incremental cost-effectiveness ratio of $61,809/quality-adjusted life-year (QALY) compared with afatinib. The acceptability curve showed that erlotinib was the optimal treatment at a willingness-to-pay threshold of $100,000/QALY (10-year population EVPI = $85.9 million). At a willingness-to-pay threshold of $50,000/QALY to $70,000/QALY (EVPI = $211.5 million-$261.8 million), however, there was considerable uncertainty whether erlotinib or afatinib was the optimal treatment.
  
  
  CONCLUSIONS
  Our analysis suggests that erlotinib is the preferred first-line treatment for advanced epithelial growth factor receptor mutation-positive non-small-cell lung cancer. Further research comparing erlotinib and afatinib is potentially justified, although accurate data are needed on the required cost and sample size of the trial.
authors.affiliation: Department of Clinical Pharmacy, University of California, San Francisco, CA, USA. Electronic address: tingj@pharmacy.ucsf.edu.
authors.forename: Jie
authors.initials: J
authors.lastname: Ting
authors.affiliation: Department of Clinical Pharmacy, University of California, San Francisco, CA, USA.
authors.forename: PharmD
authors.initials: P
authors.lastname: Tien Ho
authors.affiliation: Department of Clinical Pharmacy, University of California, San Francisco, CA, USA.
authors.forename: Pin
authors.initials: P
authors.lastname: Xiang
authors.affiliation: Department of Clinical Pharmacy, University of California, San Francisco, CA, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Sugay
authors.affiliation: Department of Clinical Pharmacy, University of California, San Francisco, CA, USA.
authors.forename: Maher
authors.initials: M
authors.lastname: Abdel-Sattar
authors.affiliation: Department of Clinical Pharmacy, University of California, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Wilson
mesh_terms: D000077716:Afatinib; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000191:economics* / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000191:economics* / Q000201:enzymology / Q000235:genetics / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics; D017326:Clinical Trials, Phase III as Topic; D057186:Comparative Effectiveness Research; D003362:Cost-Benefit Analysis; D003661:Decision Support Techniques; D018450:Disease Progression; D018572:Disease-Free Survival; D016527:Drug Costs; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000191:economics* / Q000201:enzymology / Q000235:genetics / Q000401:mortality; D008390:Markov Chains; D018803:Models, Economic; D058990:Molecular Targeted Therapy / Q000191:economics; D009154:Mutation; D018579:Patient Selection; D000068437:Pemetrexed / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics; D011788:Quality of Life; D019057:Quality-Adjusted Life Years; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors; D016896:Treatment Outcome; D035501:Uncertainty; D014481:United States
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000068437:Pemetrexed; D000077716:Afatinib; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D002945:Cisplatin
keywords: EGFR mutation-positive NSCLC; cost-effectiveness; expected value of perfect information; treatment; value-of-information