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Breast Cancer Drug Palbociclib Receives FDA ‘Breakthrough Therapy’ Designation

Combo treatment with letrozole enters phase III trial (Apr. 10)

The investigational compound palbociclib (PD-0332991, Pfizer) — an oral, selective inhibitor of cyclin-dependent kinase (CDK) 4 and 6 — has received “breakthrough therapy” designation by the FDA for the potential treatment of patients with breast cancer.

Enacted as part of the 2012 FDA Safety and Innovation Act (FDASIA), a “breakthrough therapy” designation is intended to expedite the development and review of a potential new medicine if it is “intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition, and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.”

The designation for palbociclib was based on preliminary results from a phase II trial in postmenopausal women with estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer. In this study, women treated with the combination of palbociclib plus letrozole achieved a statistically significant improvement in median progression-free survival (PFS) compared with women who received letrozole alone (26.1 months vs. 7.5 months, respectively).

A phase III randomized double-blind study is currently evaluating palbociclib in combination with letrozole versus letrozole alone as a first-line treatment in postmenopausal women with breast cancer.

Palbociclib is an investigational oral, selective inhibitor of CDK 4 and 6 — two closely related kinases that enable tumor cell progression during phase G1 to phase S in the cell cycle. This progression is necessary for DNA replication and cell division. Inhibition of CDK 4 and 6 has been shown to prevent the deactivation of retinoblastoma susceptibility gene protein (a tumor-suppressor protein) and to interfere with tumor cell progression. In preclinical studies, palbociclib was shown to be an inhibitor of cell growth and a suppressor of DNA replication by preventing cells from entering the S phase.

Source: Pfizer; April 10, 2013.

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