title: Cost-effectiveness of BRCA1 and BRCA2 mutation testing to target PARP inhibitor use in platinum-sensitive recurrent ovarian cancer.
abstract: OBJECTIVE
  (1) To determine whether use of a PARP inhibitor or (2) BRCA1/2 mutation testing followed by a PARP inhibitor for test positives is potentially cost-effective for maintenance treatment of platinum-sensitive recurrent high-grade serous ovarian cancer.
  
  
  METHODS
  A modified Markov decision analysis compared 3 strategies: (1) observe; (2) olaparib to progression; (3) BRCA1/2 mutation testing; treat mutation carriers with olaparib to progression. Progression-free survival and rates of adverse events were derived from a phase 2 randomized trial. Key assumptions are as follows: (1) 14% of patients harbor a BRCA1/2 mutation; (2) progression-free survival of individuals treated with olaparib is improved for BCRA1/2 carriers compared with noncarriers (estimated hazard ratio, approximately 0.4). Costs derived from national data were assigned to treatments, adverse events, and BRCA1/2 test. Monte Carlo probabilistic sensitivity analysis was performed.
  
  
  RESULTS
  Global olaparib was the most effective strategy, followed by BRCA1/2 testing and no olaparib. BRCA1/2 testing had an incremental cost-effectiveness ratio (ICER) of $193,442 per progression-free year of life saved (PF-YLS) compared to no olaparib, whereas global olaparib had an ICER of $234,128 per PF-YLS compared to BRCA1/2 testing. At a 52% lower-than-baseline olaparib cost estimate of $3000 per month, BRCA1/2 testing became potentially cost-effective compared with observation, with an ICER of $100,000 per PF-YLS. When strategy (1) was removed from the analysis, BRCA1/2 testing was the preferred strategy.
  
  
  CONCLUSIONS
  The use of maintenance olaparib in women with high-grade serous ovarian cancer is not cost-effective regardless of whether BRCA1/2 testing is used to direct treatment. However, BRCA1/2 testing is a preferred strategy compared to global maintenance olaparib alone.
authors.affiliation: Division of Gynecologic Oncology, Duke Cancer Institute, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC 27710, USA. secor002@mc.duke.edu
authors.forename: Angeles Alvarez
authors.initials: AA
authors.lastname: Secord
authors.forename: Jason Cory
authors.initials: JC
authors.lastname: Barnett
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Ledermann
authors.forename: Bercedis L
authors.initials: BL
authors.lastname: Peterson
authors.forename: Evan R
authors.initials: ER
authors.lastname: Myers
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Havrilesky
mesh_terms: D000970:Antineoplastic Agents / Q000191:economics / Q000627:therapeutic use; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000191:economics / Q000235:genetics / Q000401:mortality; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D009154:Mutation / Q000235:genetics*; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000191:economics* / Q000235:genetics / Q000401:mortality; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000191:economics* / Q000235:genetics / Q000401:mortality; D010793:Phthalazines / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use*; D010984:Platinum / Q000494:pharmacology*; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011379:Prognosis; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D010793:Phthalazines; D010879:Piperazines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D010984:Platinum; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; C531550:olaparib