Hypersensitivity reactions to antineoplastic agents in BRCA-mutated ovarian cancer (OC) patients: a single centre experience

Background: chemotherapy regimens with a platinum combination (mostly carboplatin and paclitaxel) have been established as the standard of care following surgery for ovarian cancer (OC), improving survival both in patients (pts) with newly diagnosed advanced OC and in pts with recurrent platinum-sensitive disease. About 10-15% of OC patients harbor a germline mutation in susceptibility genes BRCA 1/2. Patients carrying a BRCA mutation have been associated with a better prognosis and a better response to platinum-based therapy. However, hypersensitivity reactions (HSRs) to chemotherapeutic agents are common and can limit their use: HSRs to carboplatin are a particular concern, and have been reported in approximately 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 and methods: 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.Results: 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 patients 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 specifically 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 patients [9/14 (64%) vs 1/13 (8%), p = 0.004].Conclusions: 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, actually registered only for relapsed OC patients in maintenance after rechallenge of platinum-based chemotherapy. Background: chemotherapy regimens with a platinum combination (mostly carboplatin and paclitaxel) have been established as the standard of care following surgery for ovarian cancer (OC), improving survival both in patients (pts) with newly diagnosed advanced OC and in pts with recurrent platinum-sensitive disease. About 10-15% of OC patients harbor a germline mutation in susceptibility genes BRCA 1/2. Patients carrying a BRCA mutation have been associated with a better prognosis and a better response to platinum-based therapy. However, hypersensitivity reactions (HSRs) to chemotherapeutic agents are common and can limit their use: HSRs to carboplatin are a particular concern, and have been reported in approximately 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 and methods: 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. Results: 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 patients 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 specifically 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 patients [9/14 (64%) vs 1/13 (8%), p = 0.004]. Conclusions: 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, actually registered only for relapsed OC patients in maintenance after rechallenge of platinum-based chemotherapy.