Palbociclib—The First of a New Class of Cell Cycle Inhibitors

  • Marcus SchmidtEmail author
  • Martin Sebastian
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 211)


During the last decades, much has been learned about with cyclin-dependent kinases (CDK) playing a pivotal role in the cell cycle regulation. CDK4/6 is the key regulator of the G1-S transition. Palbociclib (PD 0332991, Ibrance®) is the first oral CDK4/6 inhibitor showing a substantially improved median progression-free survival (PFS) in advanced estrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) negative breast cancer. This PFS prolongation was seen both with letrozole as first-line therapy (24.8 vs. 14.5 months [PALOMA 2]) and with fulvestrant in endocrine pretreated patients (9.2 vs. 3.8 months [PALOMA-3]). The main toxicity is neutropenia due to cell cycle arrest which can be easily managed with dose interruption or dose reduction leading to a favorable safety profile with delayed deterioration of global quality of life (QoL). Palbociclib is approved by the Federal Drug Administration (FDA) and the European Medicines Agency (EMA) for ER-positive/HER2-negative advanced breast cancer. Despite the well-understood mode of action of palbociclib, predictive biomarkers are not yet defined. In conclusion, inhibition of CDK4/6 using palbociclib in combination with endocrine therapy is an efficient and well-tolerated treatment option in ER-positive/HER2-negative advanced breast cancer. Ongoing clinical trials are investigating the role of palbociclib in early breast cancer as well as in other types of cancer.


Palbocilib Breast cancer Metastatic Advanced Endocrine 


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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Obstetrics and GynecologyUniversity Medical Center MainzMainzGermany
  2. 2.Department of Hematology/Oncology, Rheumatology, HIVJ.W. Goethe UniversityFrankfurtGermany

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