Adverse event profiles of CDK4/6 inhibitors: data mining and disproportionality analysis of the FDA adverse event
Jun Shen1, Pingli Luo1, Jianmei Xu2
1Nursing Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Background:
Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors are targeted therapies designed to selectively block CDK4/6, crucial regulators of the cell cycle. These inhibitors play a pivotal role in restoring cell cycle control, particularly in breast cancer cases marked by abnormal CDK regulation, ultimately inhibiting uncontrolled cell division and tumor growth.
Objectives:
This analysis aimed to comprehensively examine adverse effects in CDK4/6 inhibitors using the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database.
Design:
Disproportionality analysis was conducted to analyze the adverse event (AE) reports related to CDK4/6 inhibitor submitted to the FAERS database.
Methods:
We collected AE reports regarding palbociclib, ribociclib, abemaciclib, trilaciclib, and dalpiciclib submitted to the FAERS from 2015Q1 to 2023Q1. We used the system organ class and the Standardized MedDRA Query to perform a comprehensive search for AEs at the preferred term (PT) level, using case reports as our data source. After removing duplicate reports, we performed disproportionality analysis and sensitivity analysis to identify safety signals.
Results:
A total of 85,635 reports encompassing 280,211 AEs were extracted for analysis. Among 3681 scrutinized PTs, approximately 484 were detected as statistically significant signals associated with CDK4/6 inhibitors. It was noteworthy that palbociclib and ribociclib had comparable safety profiles, whereas abemaciclib exhibited distinctive safety patterns. Notably, our analysis found novel safety signals linked to CDK4/6 inhibitors, including nail-related disorders such as onychoclasis, nail disorder, and nail discoloration, and psychiatric concerns, including eating disorders and emotional disorder.
Conclusion:
Overall, the present study identified several new safety signals of CDK4/6 inhibitors, as well as differences among various drugs within the CDK4/6 category, through the use of the FDA FAERS, which deserve more careful monitoring in the clinic.
Insights
Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors show new safety signals, including nail and psychiatric disorders. Analysis of FDA FAERS data revealed distinct safety profiles among CDK4/6 inhibitors, necessitating closer clinical monitoring.
Area of Science:
- Oncology
- Pharmacovigilance
- Drug Safety
Background:
- Cyclin-dependent kinases 4 and 6 (CDK4/6) are key cell cycle regulators.
- CDK4/6 inhibitors are vital targeted therapies for cancers with abnormal CDK regulation, like breast cancer.
- These therapies aim to restore cell cycle control and inhibit tumor growth.
Purpose of the Study:
- To comprehensively analyze adverse events (AEs) associated with CDK4/6 inhibitors.
- To identify novel safety signals using the FDA Adverse Event Reporting System (FAERS) database.
- To compare the safety profiles of different CDK4/6 inhibitors.
Main Methods:
- Disproportionality analysis of AE reports in the FAERS database from 2015Q1 to 2023Q1.
- Inclusion of palbociclib, ribociclib, abemaciclib, trilaciclib, and dalpiciclib.
- Systematic search using Standardized MedDRA Queries at the preferred term (PT) level, followed by disproportionality and sensitivity analyses.
Main Results:
- Analysis of 85,635 reports (280,211 AEs) identified 484 statistically significant safety signals.
- Palbociclib and ribociclib demonstrated similar safety profiles, while abemaciclib showed distinct patterns.
- Novel safety signals included nail disorders (e.g., onychoclasis, nail discoloration) and psychiatric concerns (e.g., eating, emotional disorders).
Conclusions:
- The study identified new safety signals for CDK4/6 inhibitors, including nail and psychiatric AEs.
- Differences in safety profiles exist among various CDK4/6 inhibitors.
- These findings highlight the need for enhanced clinical monitoring of CDK4/6 inhibitor-associated adverse events.
