CDK4/6 inhibitor–statin interaction and rhabdomyolysis in breast cancer treatment: a case-based systematic review

PURPOSE: Cyclin-dependent kinase (CDK) 4/6 inhibitors have significantly advanced the treatment of hormone receptor-positive, HER2-negative metastatic breast cancer, improving outcomes. However, their concurrent use with statins, a widely prescribed class of drugs, may pose a risk of rhabdomyolysis due to pharmacokinetic and pharmacodynamic interactions. This systematic review analyzes reported cases to characterize clinical presentations, therapeutic approaches, and outcomes. METHODS: A systematic search of PubMed, Embase, Scopus, and Web of Science from inception to January 2026 for case reports and case series documenting rhabdomyolysis in patients treated with CDK4/6 inhibitors. Data on demographics, clinical features, laboratory findings, management strategies, and outcomes were extracted. Quality assessment of the included cases was performed using the Joanna Briggs Institute Critical Appraisal Checklist. RESULTS: Seven case reports involving female patients aged 55-81 years were analyzed. All patients were treated for metastatic breast cancer with CDK4/6 inhibitors (ribociclib, palbociclib, or abemaciclib) alongside statins (simvastatin, atorvastatin, or rosuvastatin). Rhabdomyolysis onset ranged from 3 days to 48 months after initiation of combination therapy, or shortly after statin dose escalation in the setting of long-term CDK4/6 inhibitor use. Clinical presentations included severe myalgia, muscle weakness, and dark urine, with creatine kinase levels ranging from 3,070 to 47,000 U/L. Acute kidney injury was reported in five cases. Management primarily involved cessation of the implicated drugs and aggressive hydration, with adjunctive treatments such as corticosteroids, plasma exchange, or intravenous immunoglobulin. Five patients recovered fully, one had partial recovery with persistent renal dysfunction, and one fatality was reported. CONCLUSIONS: Rhabdomyolysis due to CDK4/6 inhibitor-statin interactions is a rare but potentially life-threatening complication. Vigilant monitoring, timely intervention, and tailored treatment strategies are essential for preventing complications and improving patient outcomes.