Related Experiment Video

Updated: Sep 19, 2025

A Three-Dimensional Spheroid Model to Investigate the Tumor-Stromal Interaction in Hepatocellular Carcinoma
12:24

A Three-Dimensional Spheroid Model to Investigate the Tumor-Stromal Interaction in Hepatocellular Carcinoma

Published on: September 30, 2021

5.4K

Hepatotoxicity across CDK 4/6 inhibitors: a Narrative Review

Wilfrid H F Wong1, Simona Vasiliu1, Thomas McFarlane2,3

  • 1School of Pharmacy, Faculty of Science, University of Waterloo, Kitchener, Canada.

Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer
|June 16, 2025
PubMed
Abstract

Insights

Ribociclib demonstrates the highest risk of liver injury among CDK4/6 inhibitors for metastatic breast cancer patients. Palbociclib shows the lowest risk, while abemaciclib

Area of Science:

  • Oncology
  • Pharmacology
  • Hepatology

Background:

  • Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are integral to treating hormone receptor-positive (HR+), human epidermal factor receptor 2-negative (HER2-) metastatic breast cancer (MBC).
  • These inhibitors, including palbociclib, ribociclib, and abemaciclib, are standard first-line therapy when combined with endocrine therapy for HR+/HER2- MBC.
  • Understanding the hepatotoxic profiles of these agents is crucial for patient safety and treatment optimization.

Purpose of the Study:

  • To systematically review and analyze the incidence rates of hepatotoxicity induced by palbociclib, ribociclib, and abemaciclib in HR+/HER2- breast cancer patients.
  • To compare the comparative incidences of drug-induced liver injury among these three CDK4/6 inhibitors.
  • To summarize current findings on CDK4/6 inhibitor-associated hepatotoxicity and suggest future research directions.

Main Methods:

  • A comprehensive literature search was conducted using PubMed and Embase databases on January 24, 2024.
  • The review included systematic reviews, meta-analyses, randomized clinical trials (RCTs), pooled safety analyses, and observational studies.
  • Data on alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) elevations (all-grade and grade ≥3) were extracted and analyzed.

Main Results:

  • Ribociclib exhibited the highest risk for both all-grade (AG) and grade ≥3 (G3+) elevations in ALAT and ASAT levels.
  • Across RCTs and pooled safety analyses, ribociclib demonstrated the highest incidence rates of AG and G3+ ALAT/ASAT elevation.
  • Palbociclib showed the highest incidence of AG ALAT/ASAT elevation in its respective analyses but the lowest risk for both AG and G3+ elevations overall.

Conclusions:

  • The review, encompassing 25 studies, suggests ribociclib is associated with the highest risk of drug-induced hepatotoxicity among the evaluated CDK4/6 inhibitors.
  • Further research is warranted to definitively confirm and precisely quantify the observed differences in hepatotoxicity incidence.
  • Comparative analysis of liver injury profiles is essential for informed clinical decision-making in HR+/HER2- MBC treatment.
Keywords:
AbemaciclibBreast cancerCyclin dependent kinasesHepatotoxicityPalbociclibRibociclib

More Related Videos

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis06:38

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis

Published on: September 12, 2019

9.0K
The CYP2D6 Animal Model: How to Induce Autoimmune Hepatitis in Mice09:03

The CYP2D6 Animal Model: How to Induce Autoimmune Hepatitis in Mice

Published on: February 3, 2012

19.4K

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.9K
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.7K
Hepatic Drug Excretion: Influencing Factors01:16

Hepatic Drug Excretion: Influencing Factors

The biliary system of the liver, crucial for bile secretion and drug excretion, comprises intrahepatic bile ducts that merge to form the common hepatic duct. This duct, carrying hepatic bile, combines with the cystic duct, draining the gallbladder and forming the common bile duct, which empties into the duodenum. Bile, produced by hepatic cells lining the bile canaliculi, is composed primarily of water, bile salts, pigments, electrolytes, and lesser amounts of cholesterol and fatty acids. Bile...
243