Palbociclib: first global approval

Palbociclib (Ibrance®) is an oral, reversible, selective, small-molecule inhibitor of cyclin-dependent kinases (CDK) 4 and CDK6 developed by Pfizer for the treatment of cancer. CDKs are important modulators of cell cycle entry and progression in response to growth signals, and inhibition of these kinases with palbociclib could enhance the activity of other anticancer drugs in tolerable regimens. Palbociclib, in combination with letrozole, was recently approved in the US for the first-line treatment of advanced breast cancer. Phase III development is underway worldwide investigating its use as first-line treatment in advanced breast cancer, as well as treatment of recurrent or advanced breast cancer and high-risk, early-stage breast cancer. A phase II trial is underway in the USA for non-small cell lung cancer under a US National Cancer Institute-funded research collaboration, and several phase I and II investigations are being conducted for various other solid tumour types and haematological malignancies. This article summarizes the milestones in the development of palbociclib leading to this first approval for use in postmenopausal women with estrogen-positive, human epidermal growth factor receptor (HER) 2-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease.