title: Cost-effectiveness of ceritinib in patients previously treated with crizotinib in anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer in Canada.
abstract: BACKGROUND
  To assess the cost-effectiveness of ceritinib vs alternatives in patients who discontinue treatment with crizotinib in anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC) from a Canadian public healthcare perspective.
  
  
  METHODS
  A partitioned survival model with three health states (stable, progressive, and death) was developed. Comparators were chosen based on reported utilization from a retrospective Canadian chart study; comparators were pemetrexed, best supportive care (BSC), and historical control (HC). HC comprised of all treatment alternatives reported. Progression-free survival and overall survival for ceritinib were estimated using data reported from single-arm clinical trials (ASCEND-1 [NCT01283516] and ASCEND-2 [NCT01685060]). Survival data for comparators were obtained from published clinical trials in a NSCLC population and from a Canadian retrospective chart study. Parametric models were used to extrapolate outcomes beyond the trial period. Drug acquisition, administration, resource use, and adverse event (AE) costs were obtained from databases. Utilities for health states and disutilities for AEs based on EQ-5D were derived from literature. Incremental costs per quality-adjusted life year (QALY) gained were estimated. Univariate and probabilistic sensitivity analyses were performed.
  
  
  RESULTS
  Over 4 years, ceritinib was associated with 0.86 QALYs and total direct costs of $89,740 for the post-ALK population. The incremental cost-effectiveness ratio (ICER) was $149,117 comparing ceritinib vs BSC, $80,100 vs pemetrexed, and $104,436 vs HC. Additional scenarios included comparison to docetaxel with an ICER of $149,780 and using utility scores reported from PROFILE 1007, with a reported ICER ranging from $67,311 vs pemetrexed to $119,926 vs BSC. Due to limitations in clinical efficacy input, extensive sensitivity analyses were carried out whereby results remained consistent with the base-case findings.
  
  
  CONCLUSIONS
  Based on the willingness-to-pay threshold for end-of-life cancer drugs, ceritinib may be considered as a cost-effective option compared with other alternatives in patients who have progressed or are intolerant to crizotinib in Canada.
authors.affiliation: a Novartis Pharmaceuticals Canada Inc, Health Policy and Patient Access , Dorval , Quebec , Canada ;
authors.forename: Manjusha
authors.initials: M
authors.lastname: Hurry
authors.affiliation: b Analysis Group , Health Economics and Outcomes Research , New York , NY , USA ;
authors.forename: Zheng-Yi
authors.initials: ZY
authors.lastname: Zhou
authors.affiliation: c Novartis Pharmaceuticals Corporation, Global Oncology Market Access & Policy , East Hanover , NJ , USA ;
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: d Analysis Group , Health Economics and Outcomes Research , Boston , MA , USA ;
authors.forename: Chenxue
authors.initials: C
authors.lastname: Zhang
authors.affiliation: d Analysis Group , Health Economics and Outcomes Research , Boston , MA , USA ;
authors.forename: Liangyi
authors.initials: L
authors.lastname: Fan
authors.affiliation: e University of Toronto, Canadian Center for Health Economics , Toronto , Ontario , Canada.
authors.forename: Mayvis
authors.initials: M
authors.lastname: Rebeira
authors.affiliation: b Analysis Group , Health Economics and Outcomes Research , New York , NY , USA ;
authors.forename: Jipan
authors.initials: J
authors.lastname: Xie
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000191:economics*; D002170:Canada; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D003362:Cost-Benefit Analysis; D000077547:Crizotinib; D018572:Disease-Free Survival; D005260:Female; D005382:Financing, Personal; D006801:Humans; D008297:Male; D008485:Medical Audit; D008875:Middle Aged; D011720:Pyrazoles / Q000191:economics* / Q000627:therapeutic use; D011725:Pyridines / Q000191:economics* / Q000627:therapeutic use; D011743:Pyrimidines / Q000191:economics* / Q000627:therapeutic use*; D019057:Quality-Adjusted Life Years; D020794:Receptor Protein-Tyrosine Kinases / Q000302:isolation & purification*; D012189:Retrospective Studies; D013450:Sulfones / Q000191:economics* / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D011720:Pyrazoles; D011725:Pyridines; D011743:Pyrimidines; D013450:Sulfones; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; C586847:ceritinib
keywords: ALK + NSCLC; Ceritinib; cost-effectiveness analysis; crizotinib; post-ALK inhibitor