title: Deleterious BRCA1/2 mutation is an independent risk factor for carboplatin hypersensitivity reactions.
abstract: BACKGROUND
  We tested the hypothesis that BRCA1/2 mutation carriers with ovarian cancer are at higher risk of carboplatin hypersensitivity reactions (HSRs).
  
  
  METHODS
  Medical records of women enrolled in two carboplatin+olaparib clinical trials (NCT01237067/NCT01445418) were reviewed. A maximum of eight cycles containing carboplatin were administered.
  
  
  RESULTS
  All women (N=87) had good performance status and end-organ function. Incidences of carboplatin HSR before enrolment and on study were 17% and 21%, respectively. Most patients who developed carboplatin HSR had a deleterious BRCA1/2 mutation (93%) vs 50% in patients without HSR (P<0.0001). Multivariable analysis accounting for potential confounding variables including age, history of allergies, and cumulative prior carboplatin cycles confirmed deleterious BRCA1/2 mutation as an independent risk factor for carboplatin HSR (odds ratio 13.1 (95% confidence interval 2.6-65.4), P=0.0017). Mutation carriers had onset of carboplatin HSR at lower cumulative exposure (P=0.003). No significant difference in outcome was observed on our study between patients with and without a history of HSR.
  
  
  CONCLUSIONS
  Deleterious BRCA1/2 mutation increased susceptibility and shortened time to carboplatin HSR, independently of other reported factors. These data suggest that at-risk women should be counselled regarding likelihood, symptoms, and potential earlier onset of carboplatin HSRs.
authors.affiliation: Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Moon
authors.forename: J-M
authors.initials: JM
authors.lastname: Lee
authors.forename: A M
authors.initials: AM
authors.lastname: Noonan
authors.forename: C M
authors.initials: CM
authors.lastname: Annunziata
authors.forename: L
authors.initials: L
authors.lastname: Minasian
authors.forename: N
authors.initials: N
authors.lastname: Houston
authors.forename: J L
authors.initials: JL
authors.lastname: Hays
authors.forename: E C
authors.initials: EC
authors.lastname: Kohn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects*; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics; D004342:Drug Hypersensitivity / Q000209:etiology / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics; D010793:Phthalazines / Q000008:administration & dosage; D010879:Piperazines / Q000008:administration & dosage; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D000970:Antineoplastic Agents; D010793:Phthalazines; D010879:Piperazines; D016190:Carboplatin; C531550:olaparib