Infection associated with CDK4/6 inhibitors: a pharmacovigilance analysis of the FDA adverse event reporting system database

Abstract

Introduction: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are first-line treatments for hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer. With their increasing clinical use, infection-related adverse events (AEs) associated with CDK4/6 inhibitors have been widely reported in recent years. This study aimed to analyze the occurrence of infections associated with the CDK4/6 inhibitors (palbociclib, ribociclib and abemaciclib) based on the real-world data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Methods: Data were extracted from the FAERS database between 2015Q1 and 2022Q3. The clinical characteristics of patients with primary suspected infection-related AEs were analyzed. A disproportionality analysis was performed to investigate the potential association between AEs and CDK4/6 inhibitors. The influencing factors were evaluated using Pearson's chi-square test.

Results: Reports of infection-related AEs associated with ribociclib accounted for 8.58% of the total reports of AEs associated with ribociclib, followed by palbociclib (2.72%) and abemaciclib (1.24%). Ribociclib (67.65%) was associated with more serious outcome events than palbociclib (30%) or abemaciclib (48.08%). The sex and age were not associated with outcome severity. Disproportionality analysis showed that fourteen, sixteen and two infection-related preferred terms were detected for palbociclib, ribociclib and abemaciclib, respectively.

Conclusion: Infection-related AEs were highly associated with three CDK4/6 inhibitors, especially palbociclib and ribociclib, based on the real-world data from the FAERS database. However, further causality assessment is required.

Keywords: CDK4/6 inhibitor; FAERS; adverse events; infection; ribociclib.

FIGURE 1

The flow chart of screening infection-related AEs for these three CDK4/6 inhibitors from 2015Q1 to 2022Q3 in the FAERS database.

FIGURE 2

ROR and 95% CI values of infection-related PTs for these three CDK4/6 inhibitors. (A) Palbociclib; (B) Ribociclib; (C) Abemaciclib.

FIGURE 3

Statistic on the occurrence of infection-related AEs for CDK4/6 inhibitors from the FAERS during 2015Q1-2022Q3. (A) Case numbers of CDK4/6 inhibitors with infection-related AEs as PS versus without infection-related AEs as PS. (B) The proportion of reports with infection-related AEs as PS or without infection-related AEs in all reports for CDK4/6 inhibitors as PS.