Palbociclib

Palbociclib, sold under the brand name Ibrance among others, is a medication developed by Pfizer for the treatment of HR-positive and HER2-negative breast cancer. It is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6. Palbociclib was the first CDK4/6 inhibitor to be approved as a cancer therapy. It is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6. In the G1 phase of the cell cycle, mammalian cells must pass a checkpoint, known as the restriction point "R", in order to complete the cell cycle and divide. CDK4 and CDK6 complex with cyclin D drive the phosphorylation of the retinoblastoma protein, Rb, which allows the cell to pass R and commit to division. Regulation of one or more proteins involved in this checkpoint is lost in many cancers. However, by inhibiting CDK4/6, palbociclib ensures that the cyclin D-CDK4/6 complex cannot aid in phosphorylating Rb. This prevents the cell from passing R and exiting G1, and in turn from proceeding through the cell cycle. Palbociclib is taken daily orally with food in a cycle of 21 days of active medication followed by 7 without. Currently palbociclib is prescribed as a combination therapy with either letrozole or fulvestrant. Patients should also not consume CYP3A inhibitors or inducers while taking palbociclib. FDA information also cautions against consuming grapefruit products while taking palbociclib. The drug was reviewed and approved under the Food and Drug Administration’s (FDA) accelerated Priority Review and Breakthrough Therapy designation programs on February 3, 2015 as a treatment (in combination with letrozole) for patients with estrogen receptor positive (ER+) advanced breast cancer. This was an accelerated approval. In March 2017, the FDA granted regular approval to palbociclib for hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative advanced or metastatic breast cancer, in combination with an aromatase inhibitor. A phase III trial, PALOMA-2, was fully enrolled by February 2015 and reported positive results in April 2016.