Abemaciclib is indicated

• in combination with endocrine therapy (ET) (tamoxifen or an aromatase inhibitor [AI]) for the adjuvant treatment of adult patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), node-positive, early breast cancer at high risk of recurrence,
• in combination with an AI as initial endocrine-based therapy for the treatment of adult patients with HR+, HER2- advanced or metastatic breast cancer (MBC),
• in combination with fulvestrant for the treatment of adult patients with HR+, HER2- advanced or MBC with disease progression following ET, and
• as monotherapy for the treatment of adult patients with HR+, HER2- advanced or MBC with disease progression following ET and prior chemotherapy in the metastatic setting.1

Abemaciclib is an inhibitor of cyclin-dependent kinase (CDK) 4 and CDK6. These kinases are activated upon binding to D-cyclins. In estrogen receptor-positive breast cancer cell lines, cyclin D1 and CDK4/6 promote phosphorylation of the retinoblastoma protein (Rb), cell cycle progression, and cell proliferation. In vitro, continuous exposure to abemaciclib inhibited Rb phosphorylation and blocked progression from G1 into S phase of the cell cycle, resulting in senescence and apoptosis. In breast cancer xenograft models, abemaciclib dosed daily without interruption as a single agent or in combination with antiestrogens resulted in reduction of tumor size.1

Abemaciclib inhibits CDK 4 and CDK6 activity with marked specificity over other CDKs (eg, CDK1, CDK2, CDK5, and CDK7) in vitro and induces G1 arrest and apoptosis in Rb-proficient cells.2,3

Abemaciclib inhibits CDK4 and CDK6 at half maximal inhibitory concentration (IC₅₀) of 2 nM and 10 nM, respectively.4-7

In cell-free biochemical assays, abemaciclib potently inhibited the kinase activity of both CDK4 and CDK6 when complexed with cyclin D family members. There was a 14-fold higher potency for inhibiting CDK4/cyclinD1 (CCND1) (0.6 nmol/L) as compared to CDK6/cyclinD3 (CCND3) (8.2 nmol/L).2,3Further analysis conducted with in-vitro cell-based assays confirmed preferential CDK4 inhibition.8,9

Preclinical results have demonstrated that a chronic or continuous dosing strategy is important for achieving durable cell-cycle arrest.4

Prolonged and continuous abemaciclib treatment led to sustained antitumor effects through inhibition of cell proliferation, altered cell metabolism, and triggered senescence and apoptosis. Treatment with abemaciclib resulted in significant inhibition of expression of genes involved in cell cycle regulation including Ki67 and longer treatment was associated with a loss of replicative capacity in breast cancer cells.3,8

An animation of the mechanism of action of abemaciclib is available here: Abemaciclib Mechanism of Action.

VERZENIO® (abemaciclib) tablets, for oral use, Lilly

The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).