Hematological toxicity of cyclin-dependent kinase 4/6 inhibitors in patients with breast cancer: a network meta-analysis and pharmacovigilance study

ABSTRACT

Objectives

We aimed to evaluate and compare the risk of hematological adverse events (AEs) associated with CDK4/6 inhibitors using data from randomized controlled trials (RCTs) and Food and Drug Adverse Event Reporting System (FAERS) database.

Methods

The PubMed, Embase, and Cochrane Library databases were searched for RCTs related to abemaciclib, palbociclib, and ribociclib. A network meta-analysis (NMA) was conducted to compare the risks of hematological AEs, and a disproportionality analysis was performed to detect signals of hematological AEs.

Results

16 RCTs comprising 16,350 breast cancer patients were included. Palbociclib and ribociclib had similar risks for hematological AEs, except a higher risk of grade 3–4 leukopenia observed with palbociclib (risk ratio [RR]: 7.84, 95% confidence interval [95%CI]: 1.33–41.28). Abemaciclib had a higher risk of anemia than both ribociclib (grade 1–4: RR: 2.23, 95% CI: 1.25 − 3.96; grade 3–4: RR: 3.52, 95% CI: 1.59 − 8.11) and palbociclib (grade 1–4: RR: 1.65, 95%CI: 1.03 − 2.59), but a lower risk of grade 3–4 of both leukopenia (RR: 0.12, 95%CI: 0.02 − 0.49) and neutropenia (RR: 0.15, 95%CI: 0.04 − 0.52) compared with palbociclib. Signals indicating occurrence of leukopenia, neutropenia, anemia, and thrombocytopenia were identified for three CDK4/6 inhibitors.

Conclusion

Abemaciclib, palbociclib, and ribociclib showed significant but inconsistent hematological toxicity risks.

KEYWORDS:

• CDK4/6 inhibitors
• hematological toxicity
• breast cancer
• FDA food and drug adverse event reporting system (FAERS) database
• network meta-analysis

Declarations of interest

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.

Reviewer disclosures

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

Author contributions

H Ding was responsible for the conception and design. Search strategy, data collection, material preparation, and data analysis were performed by H Ding, W Xu, M Dai and S Li. Wenxiu Xin, Y Tong, C He and X Mi contributed to data interpretation and data curation. W Xu and M Dai contributed to drafting the manuscript. L Fang, H Ding and Z Zhan contributed to revising it critically for important intellectual content. All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14740338.2024.2348566.

Additional information

Funding

This study was supported by the Project of Clinical Comprehensive Pharmaceutical Evaluation from Zhejiang Pharmaceutical Association under Grant [2022ZYYL11]; and Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province under Grant [2020E10021].