Abemaciclib + Endocrine Therapy for Breast Cancer

(monarchE Trial)

Recruiting at 1012 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

5637 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety and efficacy of the study drug abemaciclib in participants with high risk, node positive, early stage, hormone receptor positive (HR+), human epidermal receptor 2 negative (HER2-), breast cancer.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on certain hormone therapies or have received specific treatments like CDK4 and CDK6 inhibitors before joining.

What data supports the effectiveness of the drug Abemaciclib combined with endocrine therapy for breast cancer?

Research shows that adding Abemaciclib to endocrine therapy improves outcomes for patients with certain types of early breast cancer, specifically hormone receptor-positive and HER2-negative types. Studies found that this combination helps prevent the cancer from returning and spreading compared to using endocrine therapy alone. ^{1 2 3 4 5}

Is Abemaciclib with Endocrine Therapy safe for humans?

Abemaciclib, when used with endocrine therapy, has been studied for safety in various trials. Common side effects include neutropenia (low white blood cell count), diarrhea, and increased liver enzymes, but it is generally considered safe for treating certain types of breast cancer. ^{2 4 6 7 8}

How is the drug abemaciclib plus endocrine therapy different for breast cancer treatment?

Abemaciclib combined with endocrine therapy is unique because it specifically targets hormone receptor-positive, HER2-negative, high-risk early breast cancer, improving survival rates compared to endocrine therapy alone. This combination is particularly beneficial for patients with a high risk of recurrence, offering a new option beyond standard endocrine therapy. ^{2 3 5 9 10}

Research Team

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Eligibility Criteria

This trial is for men and women over 18 with high-risk, node-positive, early-stage HR+, HER2- breast cancer. Participants must have a tumor size of at least 5 cm or other high recurrence risk factors, be within 16 months post-surgery, and able to take oral meds. They should not have had certain prior treatments or conditions that could interfere with the study.

Inclusion Criteria

I can take pills by mouth.

Women of reproductive potential must have a negative blood pregnancy test and agree to use highly effective contraceptive methods

I have mostly recovered from the side effects of my cancer treatments and surgery.

Exclusion Criteria

My cancer has spread to distant areas or is present without lymph node involvement.

Serious preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study

I am currently on hormone therapy for reproductive reasons.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Abemaciclib combined with standard adjuvant endocrine therapy or standard adjuvant endocrine therapy alone

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 3 years

Long-term follow-up

Participants are monitored for overall survival and disease-free survival

Approximately 10 years

Treatment Details

Interventions

• Abemaciclib
• Standard Adjuvant Endocrine Therapy

Trial Overview The trial tests abemaciclib's safety and effectiveness when added to standard endocrine therapy after surgery in patients with specific types of breast cancer. It aims to see if this combination helps reduce the risk of cancer returning more than endocrine therapy alone.

Participant Groups

Group I: Endocrine Therapy Experimental Treatment 1 Intervention

Endocrine therapy (physicians' choice) standard-of-care was administered according to package label until discontinuation criteria were met.

Group II: 150 mg Abemaciclib + Endocrine Therapy Experimental Treatment 2 Interventions

Participants received Abemaciclib orally at 150 milligrams (mg) twice daily with at least 6 hours between doses for up to 2 years or until evidence of disease recurrence or other discontinuation criteria were met, whichever occurs first. Endocrine therapy (physicians' choice) standard-of-care was administered according to package label until discontinuation criteria were met.

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

NSABP Foundation Inc

Collaborator

Trials

89

Recruited

140,000+

Findings from Research

Interim results from the MONARCH3 study show that abemaciclib, a CDK4/6 inhibitor, is an effective first-line treatment for advanced ER-positive, HER2-negative breast cancer.

Patients receiving abemaciclib in combination with letrozole experienced significantly improved progression-free survival compared to those receiving a placebo with endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Abemaciclib Effective in ER+ Breast Cancer. [2019]

In a phase III trial, adding abemaciclib to adjuvant endocrine therapy significantly improved invasive disease-free survival and distant relapse-free survival in patients with hormone receptor-positive, HER2-negative, high-risk, early breast cancer.

This finding contrasts with results from a trial involving another CDK4/6 inhibitor, which did not show similar benefits, highlighting the variability in efficacy among different treatments in this class.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib Reigns Over Breast Cancer in MonarchE. [2021]

In a study involving 5637 patients with high-risk hormone receptor-positive, HER2-negative early breast cancer, the addition of abemaciclib to standard endocrine therapy significantly improved invasive disease-free survival, with a 6.4% absolute difference at 4 years.

While the treatment showed a sustained benefit in reducing recurrence risk, safety concerns were noted, including higher rates of serious adverse events and treatment-related deaths in the abemaciclib group compared to endocrine therapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Johnston, SRD., Toi, M., O'Shaughnessy, J., et al.[2023]

In a study of 396 female patients with hormone receptor positive, HER2-negative metastatic breast cancer receiving CDK4 and 6 inhibitors, the most common adverse events were neutropenia, diarrhea, and fatigue, with varying frequencies depending on the specific drug used.

The study found that while the overall incidence of adverse events was lower than in clinical trials, the rates of dose reductions and treatment holds due to these events were higher, suggesting that clinicians may be actively managing side effects to help patients continue their therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real world incidence and management of adverse events in patients with HR+, HER2- metastatic breast cancer receiving CDK4 and 6 inhibitors in a United States community setting. Price, GL., Sudharshan, L., Ryan, P., et al.[2022]

In a study involving 101 Japanese patients with advanced breast cancer, abemaciclib was found to be well tolerated, with all patients experiencing at least one treatment-emergent adverse event (TEAE), primarily manageable with interventions.

Common TEAEs included diarrhea (95.0% of patients), neutropenia (75.2%), and increased liver enzymes (ALT and AST), with most severe cases occurring early in treatment and effectively managed through dose adjustments and medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety in Japanese Advanced Breast Cancer Patients Who Received Abemaciclib in MONARCH 2 and MONARCH 3: Assessment of Treatment-Emergent Neutropenia, Diarrhea, and Increased Alanine Aminotransferase and Aspartate Aminotransferase Levels. Masuda, N., Chen, Y., Kawaguchi, T., et al.[2022]

In a phase III study involving postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer, the addition of abemaciclib to endocrine therapy significantly improved progression-free survival (PFS) compared to placebo, with a median PFS not reached versus 14.7 months in cohort A, and 11.5 months versus 5.6 months in cohort B.

Abemaciclib also demonstrated a higher objective response rate (ORR) of 65.9% in cohort A and 50.0% in cohort B compared to 36.1% and 10.5% in the placebo groups, respectively, indicating its efficacy in treating this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MONARCH plus: abemaciclib plus endocrine therapy in women with HR+/HER2- advanced breast cancer: the multinational randomized phase III study. Zhang, QY., Sun, T., Yin, YM., et al.[2022]

In a phase III trial, abemaciclib combined with endocrine therapy significantly reduced the risk of breast cancer recurrence in patients with hormone receptor positive (HR+), HER2-negative, node-positive early breast cancer, regardless of prior chemotherapy or tumor characteristics.

The combination treatment was generally well-tolerated, with manageable side effects such as diarrhea, infections, and neutropenia, making it a valuable option for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence. Fung, S., Blair, HA.[2023]

The addition of CDK4 and 6 inhibitors (like abemaciclib, palbociclib, or ribociclib) to endocrine therapy significantly improves progression-free survival and response rates in patients with HR+ and HER2- metastatic breast cancer, establishing these inhibitors as a new standard of care.

Exploratory analyses suggest that abemaciclib may be particularly beneficial for women with poor prognosis indicators, although further confirmation is needed for these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib, a CDK4 and CDK6 inhibitor for the treatment of metastatic breast cancer. Martin, M., Garcia-Saenz, JA., Manso, L., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

First-Line Abemaciclib Effective in ER+ Breast Cancer. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Abemaciclib Reigns Over Breast Cancer in MonarchE. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Abemaciclib With Endocrine Therapy for High-Risk Early Breast Cancer. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Real world incidence and management of adverse events in patients with HR+, HER2- metastatic breast cancer receiving CDK4 and 6 inhibitors in a United States community setting. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Safety in Japanese Advanced Breast Cancer Patients Who Received Abemaciclib in MONARCH 2 and MONARCH 3: Assessment of Treatment-Emergent Neutropenia, Diarrhea, and Increased Alanine Aminotransferase and Aspartate Aminotransferase Levels. [2022]

8. England pubmed.ncbi.nlm.nih.gov

MONARCH plus: abemaciclib plus endocrine therapy in women with HR+/HER2- advanced breast cancer: the multinational randomized phase III study. [2022]

9. France pubmed.ncbi.nlm.nih.gov

Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Abemaciclib, a CDK4 and CDK6 inhibitor for the treatment of metastatic breast cancer. [2021]