Hepatotoxicity After CDK 4/6 Inhibitor Initiation in the Treatment of Hormone-Positive Metastatic Breast Cancer

Area of Science:

• Oncology
• Pharmacology
• Hepatology

Background:

• Cyclin-dependent kinase (CDK) 4/6 inhibitors (ribociclib, palbociclib, abemaciclib) are vital in treating hormone-positive metastatic breast cancer, significantly enhancing progression-free survival.
• While generally well-tolerated, these inhibitors carry a risk of adverse effects, most commonly neutropenia, but also potential hepatotoxicity.

Observation:

• A 67-year-old female with metastatic invasive ductal carcinoma experienced transaminitis within 10 days of starting letrozole and ribociclib.
• Following ribociclib discontinuation, she developed elevated transaminases within two weeks of initiating palbociclib, also requiring cessation of the drug.
• Despite disease progression, the patient declined abemaciclib and has maintained stable disease on fulvestrant alone for over a year.

Findings:

• This case demonstrates severe hepatotoxicity occurring sequentially with two different CDK 4/6 inhibitors, suggesting a potential class effect.
• The patient's transaminitis necessitated the discontinuation of both ribociclib and palbociclib, underscoring the risk of hepatic injury with this drug class.

Implications:

• The findings emphasize the importance of vigilant monitoring for hepatotoxicity in patients receiving CDK 4/6 inhibitors for metastatic breast cancer.
• Clinicians must carefully weigh the established benefits of CDK 4/6 inhibitors against the risk of hepatic injury, particularly in patients with pre-existing liver conditions or those experiencing early signs of toxicity.
• Further research into predicting and managing CDK 4/6 inhibitor-induced hepatotoxicity is warranted to optimize treatment strategies for breast cancer patients.