title: Cost-Effectiveness of Treatment Sequences of Chemotherapies and Targeted Biologics for Elderly Metastatic Colorectal Cancer Patients.
abstract: BACKGROUND
  Treatment patterns for metastatic colorectal cancer (mCRC) patients have changed considerably over the last decade with the introduction of new chemotherapies and targeted biologics. These treatments are often administered in various sequences with limited evidence regarding their cost-effectiveness.
  
  
  OBJECTIVE
  To conduct a pharmacoeconomic evaluation of commonly administered treatment sequences among elderly mCRC patients.
  
  
  METHODS
  A probabilistic discrete event simulation model assuming Weibull distribution was developed to evaluate the cost-effectiveness of the following common treatment sequences: (a) first-line oxaliplatin/irinotecan followed by second-line oxaliplatin/irinotecan + bevacizumab (OI-OIB); (b) first-line oxaliplatin/irinotecan + bevacizumab followed by second-line oxaliplatin/irinotecan + bevacizumab (OIB-OIB); (c) OI-OIB followed by a third-line targeted biologic (OI-OIB-TB); and (d) OIB-OIB followed by a third-line targeted biologic (OIB-OIB-TB). Input parameters for the model were primarily obtained from the Surveillance, Epidemiology, and End Results-Medicare linked dataset for incident mCRC patients aged 65 years and older diagnosed from January 2004 through December 2009. A probabilistic sensitivity analysis was performed to account for parameter uncertainty. Costs (2014 U.S. dollars) and effectiveness were discounted at an annual rate of 3%.
  
  
  RESULTS
  In the base case analyses, at the willingness-to-pay (WTP) threshold of $100,000/quality-adjusted life-year (QALY) gained, the treatment sequence OIB-OIB (vs. OI-OIB) was not cost-effective with an incremental cost-effectiveness ratio (ICER) per patient of $119,007/QALY; OI-OIB-TB (vs. OIB-OIB) was dominated; and OIB-OIB-TB (vs. OIB-OIB) was not cost-effective with an ICER of $405,857/QALY. Results similar to the base case analysis were obtained assuming log-normal distribution. Cost-effectiveness acceptability curves derived from a probabilistic sensitivity analysis showed that at a WTP of $100,000/QALY gained, sequence OI-OIB was 34% cost-effective, followed by OIB-OIB (31%), OI-OIB-TB (20%), and OIB-OIB-TB (15%).
  
  
  CONCLUSIONS
  Overall, survival increases marginally with the addition of targeted biologics, such as bevacizumab, at first line and third line at substantial costs. Treatment sequences with bevacizumab at first line and targeted biologics at third line may not be cost-effective at the commonly used threshold of $100,000/QALY gained, but a marginal decrease in the cost of bevacizumab may make treatment sequences with first-line bevacizumab cost-effective. Future economic evaluations should validate the study results using parameters from ongoing clinical trials.
  
  
  BACKGROUND
  This study was supported in part by a grant from the Agency for Healthcare Research and Quality (R01-HS018956) and in part by a grant from the Cancer Prevention and Research Institute of Texas (RP130051), which were obtained by Du. The authors report no conflicts of interest. Study concept and design were primarily contributed by Parikh, along with the other authors. All authors participated in data collection, and Parikh took the lead in data interpretation and analysis, along with Lairson and Morgan, with assistance from Du. The manuscript was written primarily by Parikh, along with Lairson, Morgan, and Du, and revised by Parikh.
authors.affiliation: 1 RTI Health Solutions, Research Triangle Park, North Carolina, and Division of Management, Policy, and Community Health, School of Public Health, University of Texas Health Science Center at Houston.
authors.forename: Rohan C
authors.initials: RC
authors.lastname: Parikh
authors.affiliation: 2 Division of Management, Policy, and Community Health and Division of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston.
authors.forename: Xianglin L
authors.initials: XL
authors.lastname: Du
authors.affiliation: 3 Division of Management, Policy, and Community Health, School of Public Health, University of Texas Health Science Center at Houston.
authors.forename: Morgan O
authors.initials: MO
authors.lastname: Robert
authors.affiliation: 3 Division of Management, Policy, and Community Health, School of Public Health, University of Texas Health Science Center at Houston.
authors.forename: David R
authors.initials: DR
authors.lastname: Lairson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000191:economics; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000191:economics; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000191:economics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000191:economics* / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage / Q000191:economics; D001688:Biological Products / Q000191:economics* / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000191:economics; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000191:economics*; D003362:Cost-Benefit Analysis; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000191:economics; D000077150:Oxaliplatin; D019057:Quality-Adjusted Life Years; D013781:Texas
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D001688:Biological Products; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000077146:Irinotecan; D002166:Camptothecin