Musculoskeletal adverse events associated with CDK4/6 inhibitors: a real-world study using FDA Adverse Event Reporting System (FAERS) database.

Abstract

Objective: Cyclin-dependent kinase (CDK)-4/6 inhibitors have significantly improved outcomes in several cancers but can also induce various organ system toxicities, including musculoskeletal disorders. This study aimed to comprehensively characterize the musculoskeletal adverse events (MSAEs) associated with CDK4/6 inhibitors based on real-world data.

Methods: Reports of MSAEs linked to CDK4/6 inhibitors from the first quarter (Q1) of 2015 and 2023 Q4 were extracted from the FAERS. Descriptive analyses evaluated report frequencies over time and patient characteristics. Disproportionality analyses using reporting odds ratios (RORs) identified signals for specific musculoskeletal preferred terms (PTs). Time-to-onset analyses examined the temporal patterns of MSAEs.

Results: A total of 10,095 MSAE reports associated with CDK4/6 inhibitors were identified, most involving Palbociclib (n = 7819). The median age of patients was 64 years (IQR: 55-72), predominantly female (97.73%). Most reports were submitted by consumers (47.62%) and the majority of reports were from the United States (71.53%). Disproportionality analyses revealed distinct signals, with Ribociclib showing prominent signals for bone pain and bone lesions, and Abemaciclib for osteonecrosis of the jaw and pathological fractures. Palbociclib demonstrated a consistent but less pronounced signal across musculoskeletal PTs. Time-to-onset analyses demonstrated a significantly longer onset of MSAEs for Palbociclib (median 82 days, IQR[14-311]) compared to Abemaciclib (32.5 days, IQR[12-119]) and Ribociclib (34 days, IQR[8-177]) using the nonparametric Kruskal-Wallis test (P-value = 3.048e-11).

Conclusion: Musculoskeletal toxicities is a significant adverse event that affects drug safety. Early identification and proper management of these events are crucial for patients receiving CDK4/6 inhibitors. Further research is warranted to elucidate the underlying mechanisms and improve risk mitigation strategies.