CDK4-6 inhibitors in breast cancer: current status and future development.
Expert Opin Drug Metab Toxicol
; 14(11): 1123-1138, 2018 Nov.
Article
em En
| MEDLINE
| ID: mdl-30360668
ABSTRACT
INTRODUCTION:
Aberrant cellular proliferation due to dysregulation of the cyclin-dependent kinase (CDK) retinoblastoma (Rb)-pathway occurs in several cancers. Selective inhibition of CDK4/6 is an attractive target particularly in hormone-receptor positive (HR+) metastatic breast cancer (MBC), where it has transformed the treatment of these cancers in recent years. Three CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib, have been approved for the treatment of HR+, HER2 negative (HER2-) MBC. Areas covered We reviewed and compared the pharmacology, clinical efficacy, and toxicity profiles of the three CDK4/6 inhibitors and discussed several challenges in the use of these drugs, particularly in identifying biomarkers, optimizing dosing strategies, and finding best combinations with other therapies. Expert opinion All three CDK4/6 inhibitors have shown remarkable efficacy when added to endocrine therapy in the treatment of HR+/HER2- MBC with consistent improvements in progression-free survival across all phase III trials. As efficacy appears similar between the drugs, differences in toxicities, dosing schedule, and monitoring requirements may influence the choice of CDK4/6 inhibitor. There is a paucity of predictive biomarkers that have been identified thus far, but a few promising biomarkers have been studied in the preclinical setting and results of ongoing clinical studies are awaited to validate their utility.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Inibidores de Proteínas Quinases
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Expert Opin Drug Metab Toxicol
Ano de publicação:
2018
Tipo de documento:
Article