title: 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.affiliation: Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Aki
authors.initials: A
authors.lastname: Morikawa
authors.affiliation: Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan, Ann Arbor, Michigan. norahh@med.umich.edu.
authors.forename: N Lynn
authors.initials: NL
authors.lastname: Henry
mesh_terms: D047072:Aromatase Inhibitors / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors*; D018572:Disease-Free Survival; D017277:Drug Approval; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D006801:Humans; D000077289:Letrozole; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D009570:Nitriles / Q000008:administration & dosage*; D010879:Piperazines / Q000008:administration & dosage*; D011725:Pyridines / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D014230:Triazoles / Q000008:administration & dosage*
chemical_list: D047072:Aromatase Inhibitors; D014408:Biomarkers, Tumor; D051358:Cyclin-Dependent Kinase 4; D047628:Estrogen Receptor alpha; D000077289:Letrozole; D009570:Nitriles; D010879:Piperazines; D011725:Pyridines; D018719:Erb-b2 Receptor Tyrosine Kinases; D014230:Triazoles; C506487:ESR1 protein, human; C508053:ERBB2 protein, human; C495900:CDK4 protein, human; C500026:palbociclib