G Giannone1, G Scotto2, D Katsaros3, U De Giorgi4, A Farolfi4, F Borella3, S Cosma3, A Ferrero5, S Mangiacotti6, M Villa5, V Tuninetti2, E Ghisoni7, M Turinetto2, G Mittica8, S Gemmiti3, L Zavallone9, M Aglietta2, B Pasini10, M Di Maio11, G Valabrega2. 1. Candiolo Cancer Institute, FPO-IRCCS, Candiolo (TO), Italy; Department of Oncology, University of Turin, Turin, Italy. Electronic address: gaia.giannone@ircc.it. 2. Candiolo Cancer Institute, FPO-IRCCS, Candiolo (TO), Italy; Department of Oncology, University of Turin, Turin, Italy. 3. Department of Surgical Science and Gynecology, Azienda Ospedaliero Universitaria, Città della Salute, presidio S. Anna, University of Turin, Turin, Italy. 4. Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. 5. Academic Department Gynaecology and Obstetrics, University of Turin, A.O. Ordine Mauriziano, Turin, Italy. 6. University of Turin, Turin, Italy. 7. Department of Oncology, Lausanne University Hospital, Switzerland; Ludwig Institute for Cancer Research, Lausanne, Switzerland. 8. Unit of Oncology, ASL Verbano Cusio Ossola (VCO), Omegna (VB), Italy. 9. Department of Medical Oncology, Infermi Hospital, Biella, Italy. 10. Department of Medical Sciences, University of Turin, Turin, Italy. 11. Department of Oncology, A.O. Ordine Mauriziano Hospital, University of Turin, Turin, Italy.
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.
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.