Objective:

To assess the gastrointestinal (GI) safety profile of CDK4/6 inhibitors in breast cancer patients using real-world data.

Approach:

• Data Analysis: Disproportionate reporting signals of GI adverse events (AEs) were assessed using ROR, PRR, and BCPNN algorithms based on the FDA Adverse Event Reporting System database from 2004 to Q1 2025.
• Statistical Methods: Time-to-onset was analyzed using Weibull distribution, and serious vs. non-serious AE comparisons used non-parametric tests.

Key Findings:

• 63,722 reports associated with CDK4/6 inhibitors, with 18,589 involving GI AEs.
• Palbociclib had the largest proportion of CDK4/6 inhibitor-related GI AE reports, primarily involving oropharyngeal and upper GI events, with lip exfoliation and tongue blistering as its strongest signals.
• Ribociclib had the highest proportion of serious GI reports (82.38%) and 14.25% were fatal, with significant disproportionality signals for reflux gastritis and dysbiosis.
• Abemaciclib showed diarrhea as its strongest disproportionate reporting signal.
• Over 80% of positive GI pharmacovigilance signals were absent from current prescribing information.
• Median onset time for serious GI AEs varied: 15 days for abemaciclib, 27 days for ribociclib, and 49 days for palbociclib.

Interpretation:

The study identified heterogeneous disproportionate reporting patterns for GI AEs among CDK4/6 inhibitors and highlighted unlabeled pharmacovigilance signals.

Limitations:

• Findings are hypothesis-generating and not evidence of incidence or causal associations.
• Results require validation in well-designed observational or prospective studies.

Conclusion:

The study's findings require further research to validate the identified drug-event pairs.