Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors: existing and emerging differences.

Abstract

The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors palbociclib, ribociclib, and abemaciclib are standard-of-care therapy for hormone receptor-positive advanced or metastatic breast cancer, based on randomized trials showing improved progression-free survival for all 3 drugs and overall survival for ribociclib and abemaciclib. Results in early breast cancer are discordant, with sustained improvement in invasive disease-free survival demonstrated for abemaciclib but not other CDK4/6 inhibitors to date. We review nonclinical studies exploring mechanistic differences between the drugs, the impact of continuous dosing on treatment effect, and translational research into potential resistance mechanisms and prognostic and predictive markers. We focus particularly on how emerging findings may help us understand similarities and differences between the available CDK4/6 inhibitors. Even at late-stage clinical development, there remains much to learn about how agents in this class exert their varying effects.

• Authors: Stephen Johnston, Anna Emde, Carlos Barrios, Stefanie Srock, Patrick Neven, Miguel Martin, David Cameron, Wolfgang Janni, Michael Gnant
• Journal: JNCI cancer spectrum (JNCI Cancer Spectr) Vol. 7 Issue 4 (07 03 2023) ISSN: 2515-5091 [Electronic] England
• PMID: 37369022 (Publication Type: Review, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2023. Published by Oxford University Press.

Chemical References

• abemaciclib
• Aminopyridines
• CDK4 protein, human
• Cyclin-Dependent Kinase 4
• ribociclib

Topics

• Female
• Humans
• Aminopyridines (pharmacology, therapeutic use)
• Breast Neoplasms (pathology)
• Cyclin-Dependent Kinase 4 (pharmacology, therapeutic use)