Thromboembolism profiles associated with cyclin-dependent kinase 4/6 inhibitors: a real-world pharmacovigilance study and a systematic review

ABSTRACT

Background

Thrombosis is the second leading cause of mortality in cancer patients. This study aimed to investigate the association between cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) and thrombosis.

Research design and methods

A retrospective pharmacovigilance analysis based on real-world data combined with a systematic review was used to explore the thrombotic risk profiles of CDK4/6i. The study has been registered with Prospero (CRD42021284218).

Result

In the pharmacovigilance analysis, CDK4/6i showed a higher rate of reported venous thromboembolism (VTE) (ROR = 2.78, 95% CI = 2.64–2.92), with the highest signal for trilaciclib (ROR = 27.55, 95% CI = 13.43–56.52) but only 9 cases, followed by abemaciclib (ROR = 3.73, 95% CI = 3.19–4.37). For arterial thromboembolism (ATE), only ribociclib increased the reporting rate (ROR = 2.14, 95% CI = 1.91–2.41). In the meta-analysis, palbociclib, abemaciclib, and trilaciclib all increased the risk of VTE (OR = 2.23, 3.17, and 3.90). In the subgroup analysis, only abemaciclib increased the risk of ATE (OR = 2.11, 95% CI = 1.12–3.99)    .

Conclusions

CDK4/6i had different profiles of thromboembolism. Palbociclib, abemaciclib, or trilaciclib increased the risk of VTE. Ribociclib and abemaciclib showed a weak association with the risk of ATE.

KEYWORDS:

• cyclin-dependent kinase 4 and 6 inhibitors
• venous thromboembolism
• arterial thromboembolism
• pharmacovigilance
• FAERS
• systematic review

Acknowledgments

We would like to express our gratitude to Professor Xiao Chen (The First Affiliated Hospital, Sun Yat-sen University) for his expert opinions on this subject.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Data availability statement

The datasets analyzed during the current study are available in the following resource available in the public domain: https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html (accessed on 15 March 2022).

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

All authors contributed to the study conception and design. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. J Wu, M Huang, and X Yu were involved in conceptualization; Z He, Y Li, and S Gao contributed to methodology; Z He, Y Li, S Gao, J Zhu, D Liang, S Yang, J Mo, and K Lam were involved in formal analysis and investigation; Z He, Y Li, and S Gao contributed to writing-original draft preparation; Z He, Y Li, S Gao, and J Wu were involved in writing-review and editing.

Institutional review board statement

Ethical review and approval were waived for this study because it is based on anonymous data that can be downloaded from a publicly available source.

Informed consent statement

Patient consent was waived because the study is based on anonymous data that can be downloaded from a publicly available source.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14740338.2023.2181338

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.