Deleterious BRCA1/2 mutation is an independent risk factor for carboplatin hypersensitivity reactions

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. Conclusion: 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.