VERZENIO® (abemaciclib): Mechanism of Action

Indication

Abemaciclib is indicated

• in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of postmenopausal women with HR+, HER2- advanced or MBC

• in combination with fulvestrant for the treatment of women 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 regimens in the metastatic setting.¹

Mechanism of Action

Abemaciclib is an inhibitor of CDK4 and CDK6. These kinases are activated upon binding to D-cyclins. In ER+ breast cancer cell lines, cyclin D1 and CDK4/6 promote phosphorylation of the 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

Enclosed Prescribing Information

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

Reference

1. Verzenio [package insert]. Indianapolis, IN: Eli Lilly and Company; 2018.

Glossary

CDK = cyclin-dependent kinase

ER+ = estrogen receptor-positive

ET = endocrine therapy

HER2- = human epidermal growth factor receptor 2-negative

HR+ = hormone receptor-positive

MBC = metastatic breast cancer

Rb = retinoblastoma protein