Background: Carboplatin (Cp) has become the standard first-line chemotherapeutic agent for treatment of ovarian cancer (OvCa), and Cp-related hypersensitivity reaction (HSR) has been observed in 5-20% of patients (pts). The several known potential risk factors for HSR include age, # of prior platinum treatments/cycles, and longer duration of platinum-free interval (PFI). The role of BRCA mutation status has not been studied in the context of Cp HSR, although OvCa pts with BRCAmut+ are treated repeatedly with platinum-based chemotherapies.
Methods: The medical records of 74 women who enrolled and initiated at least one cycle of Cp on two phase I clinical trials (NCT01237067 and NCT01445418) with Cp and olaparib (AZD2281) were reviewed. Cp was given with olaparib for a maximum of 8 cycles. Clinical characteristics including BRCA mutation status, history of HSR prior to or on study, and outcomes were analyzed.
Results: Primary diagnoses of the 74 pts were ovarian (71), fallopian tube (1), and primary peritoneal (2) carcinomas. Pts had a median age of 56 years (27-80) and ECOG 0-1. 50/74 (68%) pts were BRCA mutation carriers (BRCA 1 , BRCA 2 , BRCA1/2 , BRCApro 68% ). All pts had received platinum-based therapy prior to enrollment, and the median # of prior platinum regimens and cycles were 2 (1-6) and 12 (2-42), respectively. The median PFI from the last prior platinum treatment to the first Cp infusion on study was 15.3 months (6-82). 15/74 (20%) pts had a documented history of HSR to Cp prior to enrollment and were pre-medicated with methylprednisolone, H1, and H2 blockers before a slow, incremental Cp infusion. 15/74 (20%) pts developed HSR on study (grade 1 , grade 2 , and grade 3 ), 4 of whom had prior history of Cp HSR. Taken together, the incidence of Cp HSR at any point in the pts’ oncologic history, either prior to or on study, was 35.1% (26/74); prior history of Cp HSR was not predictive of HSR on study. Age, median # of prior platinum cycles, and PFI for the 15 pts with HSR on study vs. those with no HSR history were 52 (27-73) vs. 56 (34-73), 12 (6-20) vs. 10 (2-42), and 21.2 (8-53) vs. 15.3 (6-82), respectively, all of which were not statistically significant. 4/15 (27%) pts with HSR on study (including 2/4 pts with prior history) stopped Cp treatment due to repeated HSR despite pre-medications, while 7/15 (47%) pts stopped therapy for other reasons. The remaining 4/15 (27%) pts successfully completed 8 cycles or are continuing therapy per protocol. BRCA mutation was significantly associated with increased risk of HSR (prior to or on study), 46% (23/50), vs. 11% (2/19) for pts with no BRCA mutation (p = 0.010).
Conclusions: Cp re-treatment can be successful for OvCa pts despite prior history of HSR. Prior HSR history did not increase the risk of HSR on study. Being a BRCAmut+ carrier was associated with a statistically significantly greater risk of HSR and may serve as a clinical predictive biomarker of Cp hypersensitivity.
Citation Format: Dominic H. Moon, John L. Hays, Christina M. Annunziata, Anne M. Noonan, Lori Minasian, Nicole Houston, Elise C. Kohn, Jung-min Lee. BRCA 1/2 mutation status is correlated with increased hypersensitivity reactions to carboplatin. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1188. doi:10.1158/1538-7445.AM2013-1188