Platinum-based chemotherapy represents the standard of care after surgery for OC, improving survival in patients (pts) with newly diagnosed advanced OC and in pts with recurrent platinum-sensitive disease. About 10-15% of OC pts has a germline mutation in BRCA 1/2 genes. Patients with BRCA mutation have a better prognosis and response to platinum-based therapy. Hypersensitivity reactions (HSRs) to chemotherapeutic agents are common and can limit their use: HSRs to carboplatin have been reported in about 15-20% of women. The aim of our study was to evaluate the incidence of HRSs to platinum compounds and other antineoplastic agents (taxanes, lyposomal anthracyclines) in BRCA-mutated OC pts.
Patients eligible for analysis were OC pts treated in Our Center from 2010 to 2015. We retrospectively collected data regarding histopathological type, treatment, HSRs and genetic testing results. We assessed the correlation between incidence of HSRs and BRCA mutation status. The analysis was performed by Fisher exact test or by Chi-square test for categorical variables.
Out of 60 OC eligible pts, BRCA was evaluated in 32 pts. Among them, 16 had a pathogenic BRCA mutation (9 pts with a BRCA2 mutation, 6 pts with a BRCA1 mutation and 1 pts with both BRCA1 and BRCA2 mutations), in 16 patients genetic testing resulted negative. In pts with BRCA-mutated OC, a significant increase in HSRs to drugs was observed [11/16 (68%) vs 4/16 (25%), p = 0.03]. Looking at the group of patients who developed HSRs to platinum-based compounds (10 total cases of HSRs in both groups, 9 in BRCA-mutated pts and 1 case in BRCA wild-type (wt) pts), a significantly higher incidence of HSRs was observed in the group of BRCA-mutated pts [9/14 (64%) vs 1/13 (8%), p = 0.004].
Our analysis suggests that BRCA mutated OC pts might have an increased incidence of HSRs compared to BRCA wt pts. This might be due to a repeated exposure to platinum-based compounds or to an increased immune reactivity in this group of pts. If confirmed, these data may complicate the use of PARP-inhibitors in BRCA-mutated pts, registered only for relapsed OC pts in maintenance after rechallenge of platinum-based chemotherapy.
Clinical trial identification
Legal entity responsible for the study
The study was coordinated by Clinica di Oncologia Medica.
This study was performed in AOU Clinica di Oncologia Medica without any external funding
All authors have declared no conflicts of interest.