Background: Hypersensitivity reactions (HSRs) to platinum are an important issue in the treatment of patients (pts) with ovarian cancer (OC). Germline BRCA mutations have been proposed as a risk factor. We aimed at evaluating the incidence and severity of HSRs to platinum in OC pts. with known BRCA status. Patients and methods: We retrospectively analyzed 432 pts. from 5 Italian Centers. In addition, we performed a systematic review and meta-analysis of published series. Results: Four hundred nine pts. received at least one prior platinum-based treatment line: 314 were BRCA wild type (77%) and 95 were BRCA mutated (23%). There was no statistical difference in exposure to platinum. Incidence of any grade HSRs was higher among BRCA mutated pts. [9% vs 18%, p = 0.019] and the time-to-HSRs curves show that the risk increases with the duration of platinum exposure, in BRCA mutated pts. more than in BRCA wild type. A multivariable analysis showed that harboring a germline BRCA mutation was related to a higher incidence of HSRs (HR: 1.84, 95% CI 1.00–3.99, p = 0.05) while having received pegylated liposomal doxorubicin (PLD) was related to a lower incidence of HSRs (HR: 0.03 95% CI 0.004–0.22, p = 0.001). The systematic review confirmed the higher incidence of HSRs in BRCA mutated pts., though heterogeneity among series was significant. Conclusions: In OC pts. with BRCA mutations, there is a significantly higher incidence of HSRs to carboplatin, not justified by longer drug exposure. On the other hand, PLD exerted a protective role in our series.

Hypersensitivity to platinum salts according to BRCA status in ovarian cancer: A retrospective analysis of clinical outcomes and systematic review of literature

Giannone G.
First
;
Scotto G.;Cosma S.;Ferrero A.;Tuninetti V.;Turinetto M.;Gemmiti S.;Aglietta M.;Pasini B.;Di Maio M.
Co-last
;
Valabrega G.
2021-01-01

Abstract

Background: Hypersensitivity reactions (HSRs) to platinum are an important issue in the treatment of patients (pts) with ovarian cancer (OC). Germline BRCA mutations have been proposed as a risk factor. We aimed at evaluating the incidence and severity of HSRs to platinum in OC pts. with known BRCA status. Patients and methods: We retrospectively analyzed 432 pts. from 5 Italian Centers. In addition, we performed a systematic review and meta-analysis of published series. Results: Four hundred nine pts. received at least one prior platinum-based treatment line: 314 were BRCA wild type (77%) and 95 were BRCA mutated (23%). There was no statistical difference in exposure to platinum. Incidence of any grade HSRs was higher among BRCA mutated pts. [9% vs 18%, p = 0.019] and the time-to-HSRs curves show that the risk increases with the duration of platinum exposure, in BRCA mutated pts. more than in BRCA wild type. A multivariable analysis showed that harboring a germline BRCA mutation was related to a higher incidence of HSRs (HR: 1.84, 95% CI 1.00–3.99, p = 0.05) while having received pegylated liposomal doxorubicin (PLD) was related to a lower incidence of HSRs (HR: 0.03 95% CI 0.004–0.22, p = 0.001). The systematic review confirmed the higher incidence of HSRs in BRCA mutated pts., though heterogeneity among series was significant. Conclusions: In OC pts. with BRCA mutations, there is a significantly higher incidence of HSRs to carboplatin, not justified by longer drug exposure. On the other hand, PLD exerted a protective role in our series.
2021
162
1
80
87
BRCA; Hypersensitivity reactions; Ovarian cancer; Platinum salts
Giannone G.; Scotto G.; Katsaros D.; De Giorgi U.; Farolfi A.; Borella F.; Cosma S.; Ferrero A.; Mangiacotti S.; Villa M.; Tuninetti V.; Ghisoni E.; Turinetto M.; Mittica G.; Gemmiti S.; Zavallone L.; Aglietta M.; Pasini B.; Di Maio M.; Valabrega G.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1793550
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