Expert consensus on optimal management of liver-related adverse events during CDK4/6 inhibitor therapy

Hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR + /HER2 -) breast cancer (BC) is the most frequently diagnosed subtype of BC, accounting for approximately 70% of cases. The introduction of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) has significantly improved clinical outcomes and transformed the therapeutic landscape of HR + /HER2 - in both the metastatic and early settings.Hepatotoxicity associated with CDK4/6i is increasingly recognized as a clinically relevant adverse event. Most cases are asymptomatic, occur early during treatment, and resolve with dose modification or management according to the Summary of Product Characteristics (SmPC). However, variability in monitoring and management persists in clinical practice. Key issues, such as corticosteroid use, treatment continuation and reintroduction of the CDK4/6i (either the same compound or another among the three globally approved agents) after liver toxicity recovery, remain insufficiently addressed by current evidence, despite the need for routine clinical decision-making.To address these gaps, a Spanish multidisciplinary panel of hepatologists and medical oncologists developed expert consensus recommendations on liver toxicity in patients with HR + /HER2 - BC receiving CDK4/6i. This consensus provides practical guidance on the classification, monitoring and management of liver-related adverse events during CDK4/6i therapy and promotes proactive collaboration between oncology and hepatology teams to support treatment continuity and optimize patient outcomes.