Cardiovascular Adverse Events Associated With New-Generation Androgen Receptor Pathway Inhibitors (ARPI) for Prostate Cancer: A Disproportionality Analysis Based on the FDA Adverse Event Reporting System (FAERS)

Yang Liu; Hui-Min Zhang; Yu Jiang; Zhi Wen; Er-Hao Bao; Jing Huang; Chong-Jian Wang; Cai-Xia Chen; Jia-Hao Wang; Xue-Song Yang

doi:10.1016/j.clgc.2023.07.003

Cardiovascular Adverse Events Associated With New-Generation Androgen Receptor Pathway Inhibitors (ARPI) for Prostate Cancer: A Disproportionality Analysis Based on the FDA Adverse Event Reporting System (FAERS)

Clin Genitourin Cancer. 2023 Oct;21(5):594-601.e2. doi: 10.1016/j.clgc.2023.07.003. Epub 2023 Jul 8.

Authors

Affiliations

¹ Department of Urology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
² Department of Urology, Chengdu Xinhua Hospital Affiliated to North Sichuan Medical College, ChengDu, China.
³ Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
⁴ Department of Urology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China. Electronic address: xuesongyang2022@163.com.

PMID: 37482524
DOI: 10.1016/j.clgc.2023.07.003

Abstract

Background: The potential cardiovascular adverse events associated with new-generation androgen receptor pathway inhibitors (ARPI) in the treatment of prostate cancer remain unclear. We aimed to assess the pharmacovigilance (PV), reporting rate, severity, and reaction outcomes of major adverse cardiovascular events (MACE) related to new-generation ARPI for prostate cancer reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS).

Methods: We analyzed reports of cardiovascular adverse events associated with drug therapy for prostate cancer submitted to FAERS between January 2014 and December 2022. Three primary new-generation ARPIs were identified: abiraterone acetate, enzalutamide, and apalutamide. Our primary composite endpoint was the PV of MACE caused by ARPIs in the treatment of prostate cancer, and the secondary endpoint was PV of other cardiovascular events. The software implemented was STATA 17.0 MP.

Results: A total of 278,031 suspected drug-adverse event pairs related to drug treatment in patients with prostate cancer were identified, of which 10,861 reports were cardiovascular events, including 5800 reports of MACE and 5061 reports of other cardiovascular events. The majority of these cardiovascular adverse event reports came from the United States (36.6%) and were mostly older men (age 76.0 ± 8.6 years). Compared with enzalutamide, the constituent ratio of MACE caused by abiraterone acetate and apalutamide was significantly increased, but the incidence of severe MACE decreased significantly. The PV signal regarding MACE was detected in abiraterone acetate and apalutamide but not in enzalutamide.

Conclusion: Abiraterone acetate and apalutamide presumably are associated with a higher risk of MACE than enzalutamide in new-generation ARPI for prostate cancer. More extensive prospective studies and more extended follow-up periods need to confirm this further.

Keywords: Abiraterone acetate; Apalutamide; Enzalutamide; Hormonal therapy; Major adverse cardiovascular event; Pharmacovigilance.