PARP inhibitor-related haemorrhages: What does the real-world study say?

Frontiers in Oncology

Oncology

Mengran Guo¹  Zhaohui Jin¹  Shiyan Wang¹  Ping Fan¹  Xiang Zhang² 

[1] Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, China;State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China;

关键词: PARP inhibitors;    haemorrhage;    FAERS database;    pharmacovigilance;    niraparib;   

DOI  :  10.3389/fonc.2023.1070343

 received in 2022-10-21, accepted in 2023-02-14,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundPARP inhibitors (PARPis) are novel molecular targeted therapeutics for inhibition of DNA repair in tumor cells, which are commonly used in ovarian cancer. Recent case reports have indicated that haemorrhages-related adverse events may be associated with PARPis. However, little is known about the characteristics and signal strength factors of this kind of adverse event.MethodsA pharmacovigilance study from January 2004 to March 2022 based on the FDA adverse event reporting system (FAERS) database was conducted by adopting the proportional imbalance method based on the four algorithms, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural networks (BCPNN) and multi-item gamma Poisson shrinker (MGPS).Results725 cases of PARPi-haemorrhages-related adverse events were identified with a fatality rate of 4.72% (30/725) and a median age of 67 years. About 88% of the adverse events occurred within 6 months, and the median duration (IQR) was 68 days. Most adverse events (n=477, 75.11%) were related to the treatment of niraparib. Importantly, niraparib exposure was associated with a significant increase in haemorrhages-related adverse events (ROR (95% CI), 1.13(1.03,1.23), PRR (χ2), 1.12(7.32), IC (IC 025), 0.17(0.15). In addition, petechiae, gingival bleeding, bloody urine, as well as rectal haemorrhage should be monitored when using niraparib.ConclusionRecognition and management of PARPi-haemorrhages-related adverse events is of significance to clinical practice. In this study, we provided a safety signal that haemorrhage-related adverse events should be monitored for when using niraparib. However, larger and more robust post-market safety studies are needed to improve the quality of this evidence.

【 授权许可】

Unknown   
Copyright © 2023 Wang, Guo, Zhang, Fan and Jin