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

• Published in: British journal of cancer Vol. 109; no. 4; pp. 1072 - 1078
• Main Authors: MOON, D. H, LEE, J.-M, NOONAN, A. M, ANNUNZIATA, C. M, MINASIAN, L, HOUSTON, N, HAYS, J. L, KOHN, E. C
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 20.08.2013
• Subjects: Adult; Age; Aged; Aged, 80 and over; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Carboplatin - administration & dosage; Carboplatin - adverse effects; Carcinoma - drug therapy; Carcinoma - genetics; Drug Hypersensitivity - etiology; Drug Hypersensitivity - genetics; Effectiveness; Female; Female genital diseases; Genes, BRCA1; Genes, BRCA2; Genetics and Genomics; Gynecology. Andrology. Obstetrics; Humans; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Multivariate Analysis; Mutation; Odds Ratio; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - genetics; Phthalazines - administration & dosage; Piperazines - administration & dosage; Retrospective Studies; Risk Factors; Tumors; Womens health; United States > US; Antineoplastic agent; ovarian cancer; Ovary cancer; Hypersensitivity; Malignant tumor; Epidemiology; Female genital diseases; Ovarian diseases; Cancerology; BRCA2 gene; deleterious BRCA1/2 mutation; Risk factor; Carboplatin; Genetics; Mutation; BRCA1 gene; Cancer; Platinum II Complexes
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2013.389

We tested the hypothesis that BRCA1/2 mutation carriers with ovarian cancer are at higher risk of carboplatin hypersensitivity reactions (HSRs). Medical records of women enrolled in two carboplatin+olaparib clinical trials (NCT01237067/NCT01445418) were reviewed. A maximum of eight cycles containing carboplatin were administered. 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. 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.