Palbociclib for the Treatment of Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer.

Abstract

Palbociclib is a selective inhibitor of cyclin-dependent kinases 4 and 6 that acts by reducing phosphorylation of the tumor suppressor gene retinoblastoma. When added to the aromatase inhibitor letrozole in a randomized phase II trial for first-line therapy of estrogen receptor-positive, HER2-negative metastatic breast cancer, palbociclib significantly increased progression-free survival compared with letrozole alone [palbociclib + letrozole: 20.2 months; 95% confidence interval (CI), 13.8-27.5; letrozole: 10.2 months; 95% CI, 5.7-12.6; HR, 0.49; 95% CI, 0.32-0.75; P = 0.0004]. On the basis of these results, the drug was recently granted accelerated approval by the FDA, and confirmatory studies are ongoing. Because this drug has a rational target in an oncologic pathway, concurrent biomarker development is of interest. In breast cancer, the most useful predictive biomarkers identified thus far are estrogen receptor and HER2 receptor status, although additional studies are ongoing. In this article, we review the development of palbociclib and its use in treatment of hormone receptor-positive metastatic breast cancer in the context of other FDA-approved agents in this setting.

• Authors: Aki Morikawa, N Lynn Henry
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 21 Issue 16 Pg. 3591-6 (Aug 15 2015) ISSN: 1557-3265 [Electronic] United States
• PMID: 26100274 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2015 American Association for Cancer Research.

Chemical References

• Aromatase Inhibitors
• Biomarkers, Tumor
• ESR1 protein, human
• Estrogen Receptor alpha
• Nitriles
• Piperazines
• Pyridines
• Triazoles
• Letrozole
• ERBB2 protein, human
• Receptor, ErbB-2
• CDK4 protein, human
• Cyclin-Dependent Kinase 4
• palbociclib

Topics

• Aromatase Inhibitors (administration & dosage)
• Biomarkers, Tumor (genetics)
• Breast Neoplasms (drug therapy, genetics, pathology)
• Cyclin-Dependent Kinase 4 (antagonists & inhibitors)
• Disease-Free Survival
• Drug Approval
• Estrogen Receptor alpha (genetics)
• Female
• Humans
• Letrozole
• Molecular Targeted Therapy
• Neoplasm Metastasis
• Nitriles (administration & dosage)
• Piperazines (administration & dosage)
• Pyridines (administration & dosage)
• Randomized Controlled Trials as Topic
• Receptor, ErbB-2 (genetics)
• Triazoles (administration & dosage)