Abemaciclib (Verzenio)

Mechanism of action

From NCI Drug Dictionary: An orally available cyclin-dependent kinase (CDK) inhibitor that targets the CDK4 (cyclin D1) and CDK6 (cyclin D3) cell cycle pathway, with potential antineoplastic activity. Abemaciclib specifically inhibits CDK4 and 6, thereby inhibiting retinoblastoma (Rb) protein phosphorylation in early G1.

Diseases for which it is used

• Breast cancer, ER-positive

History of changes in FDA indication

• 2017-09-28: FDA approved in combination with fulvestrant for women with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy. (Based on MONARCH 2)
• 2017-09-28: FDA approved as monotherapy for women and men with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting. (Based on MONARCH 1)
• 2018-02-26: FDA approved in combination with an aromatase inhibitor as initial endocrine-based therapy for postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. (Based on MONARCH 3)
• 2021-10-12: Approved with endocrine therapy (tamoxifen or an aromatase inhibitor) for adjuvant treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer at high risk of recurrence and a Ki-67 score of at least 20%, as determined by an FDA approved test. (Based on monarchE)
• 2023-03-03: Approved with endocrine therapy (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer at high risk of recurrence. (Based on monarchE; Ki-67 biomarker requirement removed)

History of changes in EMA indication

• 2018-09-26: Initial authorization as Verzenios for the treatment of women with hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative locally advanced or metastatic breast cancer in combination with an aromatase inhibitor or fulvestrant as initial endocrine-based therapy, or in women who have received prior endocrine therapy.
• 2018-09-26: Initial authorization as Verzenios for the treatment of women with hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative locally advanced or metastatic breast cancer in combination with an aromatase inhibitor or fulvestrant as initial endocrine-based therapy, or in women who have received prior endocrine therapy. In pre- or perimenopausal women, the endocrine therapy should be combined with a luteinising hormone-releasing hormone (LHRH) agonist.
• 2022-04-01: Extension of indication to include Verzenios in combination with endocrine therapy for adjuvant treatment of patients with hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive early breast cancer at high risk of recurrence.

History of changes in Health Canada indication

• 2019-04-05: Initial notice of compliance for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in combination with an aromatase inhibitor in postmenopausal women as initial endocrine-based therapy.
• 2019-04-05: Initial notice of compliance for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in combination with fulvestrant in women with disease progression following endocrine therapy. Pre- or perimenopausal women must also be treated with a gonadotropin-releasing hormone (GnRH) agonist.
• 2019-04-05: Initial notice of compliance for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer as a single agent in women with disease progression following endocrine therapy and at least 2 prior chemotherapy regimens. At least one chemotherapy regimen should have been administered in the metastatic setting, and at least one should have contained a taxane.
• 2022-01-12: New indication

History of changes in PMDA indication

• 2018-09-21: Newly indicated for the treatment of hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)negative inoperable or recurrent breast cancer.
• 2021-12-24: New indication and a new dosage for the postoperative adjuvant treatment of hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer with a high risk of recurrence.

Manufacturer Package Insert

• Abemaciclib (Verzenio) Package Insert

Also known as

• Code name: LY-2835219
• Brand names: Verzenio, Verzenios