General Information

Verzenio (abemaciclib) is a kinase inhibitor.

Verzenio is specifically indicated for use:

• In combination with fulvestrant for the treatment of women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer with disease progression following endocrine therapy
• As monotherapy for the treatment of adult patients with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting.

Mechanism of Action

Verzenio (abemaciclib) is an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4 and CDK6). These kinases are activated upon binding to D-cyclins. In estrogen receptor-positive (ER+) 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.

Side Effects

Adverse effects associated with the use of Verzenio may include, but are not limited to, the following:

• Diarrhea
• Neutropenia and leukopenia
• Nausea
• Abdominal pain
• Infections
• Fatigue
• Anemia
• Decreased appetite
• Vomiting
• Headache

Dosing/Administration

Verzenio is supplied as a tablet for oral administration. The recommended starting dose in combination with fulvestrant is 150 mg twice daily. The recommended starting dose as monotherapy is 200 mg twice daily. Continue treatment until disease progression or unacceptable toxicity. Dosing interruption and/or dose reductions may be required based on individual safety and tolerability. Please see drug label for specifications.

Clinical Trial Results

FDA Approval

The FDA approval of Verzenio was based on two studies, MONARCH 1 and MONARCH 2.

MONARCH 1: This phase 2 trial evaluated Verzenio as a monotherapy and enrolled 132 patients with HR+/HER2- metastatic breast cancer where endocrine therapy was no longer a viable option. In the study, 19.7 percent of patients taking Verzenio experienced complete or partial shrinkage of their tumors for a median 8.6 months.

MONARCH 2: This phase 3 study evaluated Verzenio in combination with Faslodex and enrolled 669 patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer randomized into two different dosing arms: 1) Verzenio in combination with Faslodex or 2) Faslodex with a placebo. The primary end point of this study was progression-free survival (PFS). Verzenio and Faslodex improved PFS compared to the Faslodex plus placebo arm, (16.4 months versus 9.3 months; p < .0000001).