Adverse Event Profiles of PARP Inhibitors: Analysis of Spontaneous Reports Submitted to FAERS

Xiaojiang Tian; Lin Chen; Di Gai; Sijie He; Xuan Jiang; Ni Zhang

doi:10.3389/fphar.2022.851246

Adverse Event Profiles of PARP Inhibitors: Analysis of Spontaneous Reports Submitted to FAERS

Front Pharmacol. 2022 Mar 25:13:851246. doi: 10.3389/fphar.2022.851246. eCollection 2022.

Authors

Xiaojiang Tian¹, Lin Chen¹, Di Gai², Sijie He³, Xuan Jiang⁴, Ni Zhang⁴

Affiliations

¹ Department of Pharmacy, Chongqing Health Center for Women and Children, Chongqing, China.
² Department of Pharmacy, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, China.
³ Department of Pharmacy, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁴ Department of Oncology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Abstract

Background: Several poly ADP ribose polymerase inhibitors (PARPis) are currently approved for the treatment of a variety of cancers. The safety profile of PARPis has not yet been systemically analyzed in the real world. We conducted this pharmacovigilance analysis using the US FDA's Adverse Event Reporting System (FAERS) database to explore the difference in adverse events (AEs) among PARPis. Methods: FAERS data (December 2014 to October 2021) were searched for reports of all FDA-approved PARPis across all indications. We used the standardized MedDRA query (SMQ) generalized search AEs on the preferred term (PT) level based on case reports. After filtering duplicate reports, disproportionality analysis was used to detect safety signals by calculating reporting odds ratios (ROR). Reports were considered statistically significant if the 95% confidence interval did not contain the null value. Results: Within the standardized MedDRA queries, significant safety signals were found, including those for olaparib [blood premalignant disorders (ROR = 17.06)], rucaparib [taste and smell disorders (ROR = 9.17)], niraparib [hematopoietic throbocytopenia (ROR = 28.2)], and talazoparib [hematopoietic erythropenia (ROR = 9.38)]. For AEs on the PT level, we found several significant signals, including platelet count decreased with niraparib (ROR = 52.78); red blood cell count decreased with niraparib (ROR = 70.47) and rucaparib (ROR = 15.09); myelodysplastic syndrome with olaparib (ROR = 35.47); acute myeloid leukaemia with olaparib (ROR = 25.14); blood pressure fluctuation with niraparib (ROR = 20.54); lymphangioleiomyomatosis with niraparib (ROR = 471.20); photosensitivity reaction with niraparib (ROR = 21.77) and rucaparib (ROR = 18.92); renal impairment with rucaparib (ROR = 33.32); and interstitial lung disease with Olaparib (ROR = 11.31). All the detected safety signals were confirmed using signals of disproportionality reporting methods. Conclusion: PARPis differed in their safety profile reports. The analysis of the FAERS database revealed significant safety signals that matched previously published case reports, including serious gastrointestinal, blood and lymphatic system, cardiovascular and respiratory complications, which require individualized drug administration according to patients' conditions.

Keywords: FDA adverse events reporting system; PARP inhibitors; adverse events; reporting odds ratios; signal detection.