title: HR+, HER2- Advanced Breast Cancer and CDK4/6 Inhibitors: Mode of Action, Clinical Activity, and Safety Profiles.
abstract: BACKGROUND
  Cyclin-dependent kinase (CDK) 4/6 inhibitor-based therapies have shown great promise in improving clinical outcomes for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer.
  
  
  OBJECTIVE
  1. Discuss the mode of action of the three CDK4/6 inhibitors in late clinical development: palbociclib (PD-0332991; Pfizer), ribociclib (LEE011; Novartis), and abemaciclib (LY2835219; Lilly). 2. Describe the efficacy and safety data relating to their use in HR+, HER2- advanced breast cancer. 3. Discuss the key side effects associated with CDK4/6 inhibitors along with considerations for adverse event management and patient monitoring.
  
  
  METHODS
  Relevant information and data were assimilated from manuscripts, congress publications, and online sources.
  
  
  RESULTS
  CDK4/6 inhibitors have demonstrated improved progression-free survival in combination with endocrine therapy compared with endocrine therapy alone. The side-effect profile of each agent is described, along with implications for patient monitoring, and considerations for patient care providers and pharmacists.
  
  
  CONCLUSIONS
  Addition of a CDK4/6 inhibitor to endocrine therapy increases efficacy and delays disease progression. Insight into the unique side-effect profiles of this class of agents and effective patient monitoring will facilitate the successful use of CDK4/6 inhibitor-based therapies in the clinic.
authors.affiliation: Department of Medicine, Duke University Medical Center, Duke University, Durham, NC. United States.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Sammons
authors.affiliation: Department of Medicine, Duke University Medical Center, Duke University, Durham, NC. United States.
authors.forename: Donna L
authors.initials: DL
authors.lastname: Topping
authors.affiliation: Duke University Medical Center, 10 Bryan Searle Drive, Suite 456B, Seeley G. Mudd Building, Durham, NC 27710. United States.
authors.forename: Kimberly L
authors.initials: KL
authors.lastname: Blackwell
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors*; D051361:Cyclin-Dependent Kinase 6 / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D058990:Molecular Targeted Therapy / Q000379:methods; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000631:Aminopyridines; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011687:Purines; D011725:Pyridines; D018719:Erb-b2 Receptor Tyrosine Kinases; D014157:Transcription Factors; C490267:HR protein, human; C000590451:abemaciclib; C508053:ERBB2 protein, human; C495900:CDK4 protein, human; C495911:CDK6 protein, human; C500026:palbociclib; C000589651:ribociclib
keywords: Abemaciclib; CDK4/6 inhibitor; advanced breast cancer; hormone receptor-positive; palbociclib; ribociclib