Management of Severe Abemaciclib-induced Liver Dysfunction: Feasibility of Switching to Palbociclib

Abemaciclib, a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, can cause severe liver injury, leading to treatment discontinuation. We report five cases of patients treated with a combined regimen of a CDK4/6 inhibitor and hormone therapy for metastatic breast cancer. Following the development of serious liver dysfunction (grade ≥3) during abemaciclib therapy, switching to palbociclib allowed continuation of CDK4/6 inhibitor treatment.

The causative role of abemaciclib was assessed using the drug-induced liver injury scoring system (RECAM-J 2023), which evaluates multiple factors, including time to onset, course after onset, prior reports of liver injury, exclusion of other potential causes, and effects of re-administration. A score of ≥8 indicates a high likelihood of drug-induced liver injury; all five cases in this study met this criterion, with one case reaching a maximum score of 17. Because CDK4/6 inhibitors are administered alongside hormonal agents, we also evaluated the potential contribution of concomitant endocrine therapy. The likelihood of hormonal agents causing liver injury was assessed as "Possible." Each patient underwent further hepatological evaluation, including testing for viral hepatitis and autoimmune hepatitis. Based on these assessments, the hepatologist confirmed drug-induced liver injury. injury. Following normalization of liver function test values, patients were switched to palbociclib. No recurrence of liver dysfunction was observed, allowing CDK4/6 inhibitor therapy to continue successfully.

These cases suggest that severe liver damage induced by abemaciclib, does not necessarily preclude continued CDK4/6 inhibitor therapy. Switching to palbociclib may be a feasible strategy, provided liver function has recovered before reinitiating treatment.