Abemaciclib + Endocrine Therapy for Breast Cancer

(monarchE Trial)

Not currently recruiting at 1127 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Must be taking: Endocrine therapy

Must not be taking: CDK4/6 inhibitors, Reproductive hormones

Disqualifiers: Metastatic disease, Inflammatory breast cancer, others

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for breast cancer using abemaciclib, a type of targeted therapy, alongside standard hormone therapy. It focuses on individuals with early-stage, hormone receptor-positive (HR+) breast cancer that lacks the HER2 protein. The trial aims to determine if this combination is more effective and safe for those who have undergone surgery and are at higher risk of recurrence, such as those with large tumors or multiple affected lymph nodes. Participants must have completed surgery and be free of distant metastases (cancer spread to other body parts). As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that abemaciclib, the drug used in this trial, is generally well-tolerated by patients. Patients report that any side effects are usually manageable and tend to resolve. If side effects occur, they often disappear once the treatment stops.

In earlier studies with abemaciclib, patients with early breast cancer did not encounter long-term safety issues, suggesting the treatment is relatively safe for this type of cancer.

Overall, evidence suggests that abemaciclib is a safe option for those considering participation in a clinical trial with this drug. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Unlike the standard of care for breast cancer, which typically involves endocrine therapy alone, Abemaciclib is an exciting addition because it targets cancer cells differently. Abemaciclib is a CDK4/6 inhibitor, which means it works by disrupting the cancer cell division cycle, potentially reducing cancer cell growth and spread. Researchers are particularly enthusiastic about Abemaciclib because it offers a novel mechanism of action that could enhance the effectiveness of traditional endocrine therapies, potentially leading to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for breast cancer?

This trial will compare the effects of adding abemaciclib to standard hormone therapy versus using hormone therapy alone for high-risk, early-stage breast cancer. Research has shown that combining abemaciclib with hormone therapy reduced the risk of death by 15.8% compared to hormone therapy alone. After two years of treatment, 92.6% of participants taking abemaciclib with hormone therapy were still alive, compared to 89.4% of those using only hormone therapy. At the three-year mark, the survival rate was 88.9% with abemaciclib versus 83.7% without it. These findings suggest that abemaciclib may significantly improve survival for breast cancer patients. ^{3 6 7 8 9}

Who Is on the 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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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 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]

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]

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]

Citations

1. onclive.com onclive.com/view/abemaciclib-plus-endocrine-therapy-provides-os-benefit-in-hr-her2-negative-breast-cancer

Abemaciclib Plus Endocrine Therapy Provides OS Benefit ... Abemaciclib plus endocrine therapy reduced death risk by 15.8% in high-risk early breast cancer patients compared to endocrine therapy alone.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12550314/

metastatic breast cancer: A propensity-matched ... In this large, real-world cohort study, first-line abemaciclib was associated with a significant overall survival benefit compared to ...

3. prnewswire.com prnewswire.com/news-releases/lillys-verzenio-abemaciclib-prolonged-survival-in-hr-her2--high-risk-early-breast-cancer-with-two-years-of-treatment-302586849.html

Lilly's Verzenio® (abemaciclib) prolonged survival in HR+, ... In high-risk EBC, Verzenio has shown a persistent and deepening benefit beyond the two-year treatment period in the monarchE trial, an adjuvant ...

4. verzenio.lilly.com verzenio.lilly.com/hcp/efficacy-early-breast-cancer

Verzenio® + ET for Early Breast Cancer | Efficacy - Eli Lilly At Month 24, Verzenio plus ET was 92.6% vs ET alone at 89.4%—a 2-year delta of 3.2%. At Month 36, Verzenio plus ET was 88.9% vs ET alone at 83.7%—a 3-year delta ...

5. thelancet.com thelancet.com/journals/lanepe/article/PIIS2666-7762(25)00263-7/fulltext

Prevalence and prognosis of patients with breast cancer ... In this study, we describe the nationwide prevalence and outcomes of patients with breast cancer in Sweden who would be candidates for adjuvant abemaciclib or ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03155997

Study Details | NCT03155997 | Endocrine Therapy With or ... 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, ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0923753425049488

Overall Survival with Abemaciclib in Early Breast Cancer Patient reported outcomes findings confirm a tolerable and reversible toxicity profile. The long-term safety data compiled did not support any ...

8. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK609559/

Abemaciclib (Verzenio) - NCBI Bookshelf - NIH In patients with HR-positive, HER2-negative early-stage breast cancer, the 5-year survival rate is greater than 90%. Although patients with early-stage breast ...

9. empr.com empr.com/news/abemaciclib-improves-overall-survival-in-hr-her2-high-risk-early-breast-cancer/

Abemaciclib Improves Overall Survival in HR+, HER2-, ... Newly released findings showed abemaciclib plus endocrine therapy statistically significantly improved OS vs endocrine therapy alone after 2 ...