title: Sequential Therapies and the Cost-Effectiveness of Treating Metastatic Colon Cancer Patients.
abstract: BACKGROUND
  Technological advances in colon cancer treatment have significantly increased survival outcomes among metastatic patients. With different chemotherapy and biologic regimens administered in first, second, and subsequent lines of treatments, costs and survival outcomes vary considerably. However, there is little evidence on how the type of regime administered in the first line of treatment affects the costs and survival outcomes of the second line of treatment.
  
  
  OBJECTIVE
  To examine how the cost-effectiveness of second-line treatment for elderly metastatic colon cancer patients varies by the type of regimen administered in the first line of treatment.
  
  
  METHODS
  The Surveillance, Epidemiology and End Results (SEER) cancer registry was used, which is linked with the Medicare claims database, to study elderly metastatic patients diagnosed between 2003 and 2009. Average survivals are estimated using the robust nonparametric Kaplan-Meier method. Selection bias was adjusted for using inverse probability weighting and censoring using robust nonparametric methods of estimating the average of total health care costs.
  
  
  RESULTS
  Mean incremental survival was 6.7 months for patients who received second-line treatment (95% CI = 5.7-7.7) compared with those receiving only first-line treatment. However, the mean incremental survival varied between 4 months (95% CI = 0.0-7.3) and 9 months (95% CI = 6.5-11.0) depending on whether fluorouracil with or without leucovorin, irinotecan, oxaliplatin, or other agents were administered in first-line treatment. The mean incremental cost associated with receipt of second-line treatment was $60,231 (95% CI = 52,461-64,198) but ranged between $55,368 (95% CI = 48,294-61,290) and $71,211 (95% CI = 43,168-99,667), depending on the type of regimen administered in the first-line treatment. Combining survival benefits and costs, the incremental cost-effectiveness ratios per life-year gained associated with the receipt of second-line treatment were $97,368 (95% CI = 80,415-117,965); $110,621 (95% CI = 89,560-133,961); $130,689 (95% CI = 101,459-171,918); and $247,951 (95% CI = 112,629808,976) when irinotican, fluorouracil/leucovorin, oxaliplatin, and "other" combinations were, respectively, administered in first-line treatment. In addition, the results varied depending on which statistical method was used.
  
  
  CONCLUSIONS
  When therapies are administered in a sequential manner, the cost-effectiveness of the second line of therapy depends on what was administered in the first line of therapy.
  
  
  BACKGROUND
  Bayer Healthcare Pharmaceuticals provided funding for this project. Onukwugha has received research funding from Bayer and Amgen and has a consultant/advisory relationship with Jansen Analytics at Johnson & Johnson. Seal was formerly an employee of Bayer and holds stock in Bayer. Mullins has research funding sponsored by Bayer and Pfizer and has a consultant/advisory relationship with Bayer, Amgen, BMS, Genentech, GSK, Novartis, NovoNordisk, and Pfizer. Woldemichael and Nader report no conflicts of interest. All authors contributed to the concept and design of this study. Onukwugha, Seal, and Mullins collected the data, with assistance from Woldemichael and Hanna, while Woldemichael interpreted the data, assisted by the other authors. The manuscript was written primarily by Woldemichael, with assistance from the other authors, and revised by Seal, Hanna, and Mullins, with assistance from Woldemichael and Onukwugha.
authors.affiliation: 1 Department of Pharmaceutical Health Services, University of Maryland School of Pharmacy, Baltimore.
authors.forename: Andinet
authors.initials: A
authors.lastname: Woldemichael
authors.affiliation: 2 Pharmaceutical Health Services Research, University of Maryland School of Pharmacy, Baltimore.
authors.forename: Eberechukwu
authors.initials: E
authors.lastname: Onukwugha
authors.affiliation: 3 Bayer Healthcare Pharmaceuticals, Wayne, New Jersey.
authors.forename: Brian
authors.initials: B
authors.lastname: Seal
authors.affiliation: 4 Department of Surgery, Division of General and Oncologic Surgery, University of Maryland School of Medicine, Baltimore.
authors.forename: Nader
authors.initials: N
authors.lastname: Hanna
authors.affiliation: 2 Pharmaceutical Health Services Research, University of Maryland School of Pharmacy, Baltimore.
authors.forename: C Daniel
authors.initials: CD
authors.lastname: Mullins
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000191:economics*; D015331:Cohort Studies; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000191:economics* / Q000401:mortality; D003362:Cost-Benefit Analysis / Q000191:economics* / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D012042:Registries; D018426:SEER Program / Q000191:economics*; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome