Abstract
The historical median survival of advanced luminal breast cancer does not exceed four years. The deciphering of the mechanisms of resistance to hormone therapy has led to the development of inhibitors of cyclin D dependent kinases (CDK4 and 6). Three drugs, palbociclib, ribociclib and abemaciclib, very similar pharmacologically, have been evaluated in the context of pivotal, randomized phase III trials. Strikingly and regardless of the endocrine therapy backbone, and in both hormone-sensitive and hormone-resistant patients, the addition of a CDK4 / 6 inhibitor doubles progression-free survival with a hazard ratio always around 0.55. The benefit in overall survival begins to be demonstrated. This review presents all published results, as well as the main safety data.
Keywords:
Advanced breast cancer; CDK4/6 inhibitor; Cancer du sein avancé; Inhibiteur de CDK4/6.
Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.
MeSH terms
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Aminopyridines / therapeutic use
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Benzimidazoles / therapeutic use
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Breast Neoplasms / drug therapy*
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Breast Neoplasms / enzymology
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Breast Neoplasms / mortality
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Breast Neoplasms / pathology
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Cell Cycle
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Clinical Trials, Phase III as Topic
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Cyclin-Dependent Kinase 4 / antagonists & inhibitors*
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Cyclin-Dependent Kinase 4 / metabolism
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Cyclin-Dependent Kinase 6 / antagonists & inhibitors*
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Cyclin-Dependent Kinase 6 / metabolism
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Female
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Humans
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Piperazines / therapeutic use
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Progression-Free Survival
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Proportional Hazards Models
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Protein Kinase Inhibitors / therapeutic use*
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Purines / therapeutic use
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Pyridines / therapeutic use
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Randomized Controlled Trials as Topic
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Retinoblastoma Binding Proteins / metabolism
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Ubiquitin-Protein Ligases / metabolism
Substances
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Aminopyridines
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Benzimidazoles
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Piperazines
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Protein Kinase Inhibitors
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Purines
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Pyridines
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RB1 protein, human
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Retinoblastoma Binding Proteins
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abemaciclib
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Ubiquitin-Protein Ligases
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CDK4 protein, human
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CDK6 protein, human
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Cyclin-Dependent Kinase 4
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Cyclin-Dependent Kinase 6
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palbociclib
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ribociclib