Real-world pharmacovigilance study of myelotoxicity with PARP inhibitors in breast and ovarian malignancies.

Abstract

e23299 Background: Poly ADP-ribose polymerase inhibitors (PARPi) revolutionized the management of BRCA1/2-mutated breast and ovarian cancers by targeting the DNA damage repair defects. Ongoing studies aim to understand better their mechanisms and adverse events (AE) profiles. Myelosuppression and progression to hematological malignancies remain an ongoing concern with PARPi. In this study, we aimed to analyze and compare the reports of myelotoxicity among different PARPi approved in breast and ovarian cancer using the United States Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: We queried the FAERS database for Olaparib, Rucaparib, Niraparib, Talazoparib, and AEs reported between 2016-2024 were categorized. Outcomes of interest were grouped into myelosuppression, progression to acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Descriptive statistics were performed, and disproportionality analysis was conducted by calculating the reportable odds ratio (ROR) with 95% confidence intervals (CIs). ROR was considered significant when the lower limit of the 95% CI was greater than 1. Results: A total of 15,558 AEs were reported with Olaparib, 8,523 with Rucaparib, 20,325 with Niraparib, and 1,177 with Talazoparib. Among those reporting myelosuppression, the highest number of reports was for Olaparib, followed by Niraparib, Rucaparib, and Talazoparib. For myelosuppression, the number of reports in ovarian cancer were 140 for Olaparib, 95 for Niraparib and 32 for Rucaparib. In breast cancer, there were 15 reports for Olaparib, 11 for Rucaparib, and 7 for Talazoparib. The ROR for MDS was highest with Olaparib, followed by Talazoparib, Niraparib, and Rucaparib. For AML, the ROR was highest with Olaparib, followed by Niraparib, Rucaparib, and Talazoparib (Table 1). Conclusions: Olaparib has the highest incidence for myelotoxicity, AML and MDS among the different PARPi in breast and ovarian cancer. Close monitoring is essential for patients receiving PARPi, with early recognition and management of myelosuppression crucial to preventing progression to hematological malignancies. Myelotoxicity outcomes with different PARP inhibitors. PARPi Olaparib Rucaparib Niraparib Talazoparib Myelosuppression  N 354 52 147 11  ROR (95% CI) 22.3 (20.1,24.8) 5.99 (4.5,7.8) 7.10 (6.0,8.3) 9.1 (5.07,16.6) MDS  N 431 22 123 9  ROR (95% CI) 59.9 (54.4,66.0) 5.5 (3.6,8.4) 13.0 (10.9,15.6) 16.5 (8.5,31.8) AML  N 293 32 107 3  ROR (95% CI) 37.9 (33.7,42.6) 7.5 (5.3,10.7) 10.6 (8.7,12.8) 5.1 (1.6,15.9)