Abemaciclib (Verzenio)

Approved for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer that has progressed after endocrine therapy.

Approved for hormone receptor positive and HER2 negative patients with tumors with KI 67 expression of 20% or higher.


Abemaciclib is an oral, continuously dosed CDK4/6 inhibitor that is currently approved by the FDA for the treatment of patients with hormone receptor-positive/HER2-negative advanced or metastatic breast cancer in combination with a nonsteroidal, fulvestrant, or as monotherapy.


A CDK4/6 inhibitor that produces a response rate of approximately 20% as monotherapy for heavily pretreated patients with refractory hormone receptors positive, HER2 negative advanced breast cancer (MONARCH 1 trial).

The third approved cyclin-dependent kinase (CDK) 4/6 inhibitor.

It exhibits unique and potentially advantageous therapeutic activity over other CDK4/6 inhibitors.

Provides a new targeted treatment option for certain patients with breast cancer who are not responding to treatment, and unlike other drugs in the class, it can be given as a stand-alone treatment to patients who were previously treated with endocrine therapy and chemotherapy,

MONARCH 2 clinical trial, abemaciclib in combination with fulvestrant were compared with placebo and fulvestrant in a randomized trial of 669 patients with HR-positive, HER2-negative breast cancer who had progressed on endocrine therapy and had not received chemotherapy since the cancer had metastasized.

In the MONARCH 2 trial there was a 45% decrease in risk of disease progression compared to fulvestrant alone-median progression free time for combination was 16.4 months vs. 9.3 months for fulvestrant alone.

Abemaciclib Plus fulvestrant improves overall survival in hormone receptor positive/HER2 negative advanced breast cancer: at 47.7 months to follow up the median overall survival with the combination of drugs was 46.7 months compared with 37.3 months for a placebo plus fulvestrant.

Treatment with abemaciclib (Verzenio) and standard endocrine therapy reduced the risk of invasive disease recurrence or death by 28.7%, compared with endocrine therapy alone, in patients with high-risk, early hormone receptor-positive, HER2-negative breast cancer, 

according to findings from a primary outcome analysis of the phase 3 monarchE trial.


Abemaciclib combined with standard endocrine therapy demonstrated a reduction in the risk of developing iDFS and distant relapse-free survival events for patients with hormone receptor-positive, HER2-negative, high-risk early breast cancer, and resulted in a statistically significant improvement in invasive DFS in patients with high Ki-67 tumors.

These inhibitors are used as frontline medications for patients with advanced, HR+/HER2- breast cancers.

Abemaciclib exhibits unique therapeutic activity that could help inform the design of better treatment strategies, including optimized combination therapies and circumventing drug resistance.

Abemaciclib may unexpectedly work in patients who are not responsive to other drugs in the class.

Following disease progression on palbociclib patients with hormone receptor positive metastatic breast cancer manifest clinical benefit in almost 37% of patients suggesting that some patients may benefit from continued CDK4/6 directed therapy.

Of CDK inhibitors only abemaciclib causes significant cancer cell death at high doses, suggesting the drug may be affecting proteins other than only CDK4/6.

In the monarchE trial, patients with hormone receptor-positive/HER2-negative, node-positive, high-risk early breast cancer were enrolled onto 1 of 2 cohorts: 1 was based on clinicopathological risk factors, which included 4 or more positive axillary lymph nodes (ALN) or 1 to 3 ALNs and at least a grade 3 histology or a tumor size 5 cm or larger; the second cohort was based on Ki-67 status and comprised patients with 1 to 3 ALNs, a centrally tested Ki-67 index of 20% or higher, no grade 3 histology, and a tumor size below 5 cm.

Patients were randomized 1:1 to receive standard endocrine therapy for 5 to 10 years as clinically indicated alone or with abemaciclib at 150 mg twice daily for up to 2 years.

MonarchE trial found  abemaciclip added to endocrine therapy resulted in an increase in absolute invasive disease free survival and distant free survival benefit at four years and confirmed its use with endocrine therapy in reducing the risk of recurrence with patients with high risk hormone receptor positive HER2 negative, node positive early breast cancer.


Results showed that abemaciclib reduced the risk of invasive disease by 25.3% versus endocrine therapy alone (HR, 0.747).


Additionally, the 2-year DFS rates were 92.2% in the abemaciclib arm versus 88.7% in the endocrine-alone arm, reflecting an absolute improvement of 3.5%.


In the Ki-67-high population, the risk of developing an DFS event was reduced by 30.9% with abemaciclib (HR, 0.691).


The 2-year DFS rates were 91.6% with abemaciclib and 87.1% with endocrine therapy alone, which translated to a 4.5% difference.


When evaluating for distant disease free survival  (DRFS)  the intent to treat population, results showed that abemaciclib reduced the risk of DRFS by 31.3% versus endocrine therapy (HR, 0.687) which was a clinically meaningful benefit. 


The 2-year DRFS rates were 93.8% and 90.8%, which was a 3.0% difference favoring abemaciclib.


MonarchE trial, 5637 patients with high-risk, node-positive, ER-positive, HER2-negative breast cancer are randomized to receive 5 to 10 years of adjuvant ET, with or without the addition of 2 years of the CDKI abemaciclib.


Subanalysis of cohort 1, the addition of abemaciclib to ET reduced the risk of IDFS by 35.7% compared with ET alone in patients with a high baseline Ki-67 index (>20%). 


 Most  common adverse reactions: diarrhea, fatigue, and neutropenia.


Rare AEs included interstitial lung disease and venous thromboembolism.


This trial shows improved invasive disease-free survival for the addition of abemaciclib to standard endocrine therapy in a very high-risk group of patients with hormone receptor-positive breast cancer. 


This class of inhibitors is largely cytostatic rather than cytocidal, meaning that it blocks cell proliferation rather than killing the cells. 


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