Palbociclib: A Novel Cyclin-Dependent Kinase Inhibitor for Hormone Receptor-Positive Advanced Breast Cancer

Ann Pharmacother. 2015 Nov;49(11):1252-60. doi: 10.1177/1060028015602273. Epub 2015 Aug 31.


Objective: To review palbociclib, a novel small-molecule inhibitor of cyclin-dependent kinases 4 and 6, and its current place in therapy for the treatment of hormone receptor (HMR)-positive, human epidermal growth factor receptor 2 (Her2)-negative advanced breast cancer.

Study selection and data abstraction: Four phase I trials, 2 phase II trials, and 1 phase III trial were identified from May 2004 to May 2015 using PubMed, American Society of Clinical Oncology (ASCO) abstracts, and European Society of Medical Oncology (ESMO) abstracts.

Data synthesis: In the first-line setting, the phase II PALbociclib: Ongoing trials in the Management of breast cAncer (PALOMA)-1 trial randomized patients to receive letrozole alone or letrozole plus palbociclib 125 mg daily for 3 weeks, followed by 1 week off, as initial therapy for advanced breast cancer. The investigator-assessed median progression-free survival (PFS) was 20. 2 months for the combination versus 10.2 months for letrozole alone (hazard ratio [HR] = 0.488; 95% CI = 0.319-0.748; 1-sided P = 0.0004). The ensuing Food and Drug Administration approval of palbociclib was given a "breakthrough therapy" designation, where preliminary evidence suggests substantial improvement over existing therapies for a serious or life-threatening disease. A confirmatory phase III trial, PALOMA-2, is under way. In patients who were previously treated with endocrine therapy for advanced breast cancer, the phase III PALOMA-3 trial randomized patients to fulvestrant plus palbociclib versus fulvestrant plus placebo. The investigator-assessed median PFS at the time of a preplanned analysis was 9.2 months with palbociclib-fulvestrant compared with 3.8 months with placebo-fulvestrant (HR = 0.42; 95% CI = 0.32-0.56; P < 0.001).

Conclusions: Palbociclib, the first-in-class CDK4/6 inhibitor, significantly extended PFS in combination with endocrine therapy in the first and subsequent lines of treatment for HMR-positive, Her2-negative advanced breast cancer.

Keywords: CDK inhibitor; PD-0332991; advanced breast cancer; fulvestrant; letrozole; palbociclib.

Publication types

  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Cyclin-Dependent Kinases / antagonists & inhibitors*
  • Disease-Free Survival
  • Estradiol / analogs & derivatives
  • Estradiol / therapeutic use
  • Female
  • Fulvestrant
  • Humans
  • Letrozole
  • Neoplasms, Hormone-Dependent / drug therapy
  • Nitriles / administration & dosage
  • Piperazines / therapeutic use*
  • Pyridines / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Receptor, ErbB-2 / metabolism
  • Triazoles / administration & dosage
  • United States


  • Nitriles
  • Piperazines
  • Pyridines
  • Triazoles
  • Fulvestrant
  • Estradiol
  • Letrozole
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Cyclin-Dependent Kinases
  • palbociclib