Abemaciclib + Fulvestrant for Breast Cancer

(MONARCH 2 Trial)

Recruiting at 267 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 28

Duration: 9 months

669 Participants Needed

Trial Summary

What is the purpose of this trial?

The main purpose of this study is to compare progression-free survival for women with hormone receptor positive (HR+), human epidermal growth factor receptor (HER2) negative advanced breast cancer receiving either abemaciclib + fulvestrant or fulvestrant alone. Participants will be randomized to abemaciclib or placebo in a 2:1 ratio. The study will last about 9 months for each participant. For the endocrine naïve cohort, all participants will received abemaciclib + fulvestrant.

Do I need to stop my current medications to join the trial?

The trial requires that you stop previous cancer therapies, such as aromatase inhibitors, anti-estrogens, chemotherapy, radiotherapy, and immunotherapy, at least 14 to 21 days before starting the study drug. However, the protocol does not specify if you need to stop other non-cancer medications.

What data supports the effectiveness of the drug combination of Abemaciclib and Fulvestrant for breast cancer?

Research shows that the combination of Abemaciclib and Fulvestrant significantly improves progression-free survival and overall survival in patients with hormone receptor-positive, HER2-negative advanced breast cancer compared to Fulvestrant alone. This means patients lived longer without their cancer getting worse and had a longer overall survival time. ^{1 2 3 4 5}

Is the combination of Abemaciclib and Fulvestrant safe for humans?

The combination of Abemaciclib and Fulvestrant has been studied in breast cancer patients and is generally considered safe, though it can cause side effects like diarrhea, infections, and low white blood cell counts. These side effects are usually manageable. ^{1 3 6 7 8}

How is the drug Abemaciclib + Fulvestrant unique for breast cancer treatment?

Abemaciclib combined with Fulvestrant is unique because it targets hormone receptor-positive, HER2-negative advanced breast cancer by inhibiting specific proteins (CDK4/6) that help cancer cells grow, and it has shown to significantly improve progression-free survival compared to Fulvestrant alone, especially in patients resistant to endocrine therapy. ^{1 3 4 5 9}

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 postmenopausal women with HR+, HER2- advanced breast cancer who haven't had more than one endocrine therapy or any chemo for metastatic disease. They must have a good performance status, no central nervous system metastasis, and not be in another conflicting study.

Inclusion Criteria

I have never received hormone therapy for my current or any previous cancer.

I am not pregnant and agree to use birth control during and 12 weeks after the study if my menopause is due to treatment.

My cancer can be measured by tests or is only in my bones.

Exclusion Criteria

I have not taken any experimental drugs recently.

I recently got a yellow fever vaccine.

I have had heart problems in the last year.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive abemaciclib or placebo in combination with fulvestrant. Abemaciclib or placebo is administered orally every 12 hours on Days 1 to 28 of a 28-day cycle, and fulvestrant is administered intramuscularly on specific days.

9 months

Regular visits every 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 31 months

Treatment Details

Interventions

• Abemaciclib
• Fulvestrant
• Placebo

Trial Overview The study tests if adding Abemaciclib to Fulvestrant improves progression-free survival compared to Fulvestrant alone in these patients. Participants are randomly assigned to receive either the combination or just Fulvestrant over about 9 months.

Participant Groups

Group I: Abemaciclib + Fulvestrant Experimental Treatment 2 Interventions

Abemaciclib 150 milligram (mg) administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.

Group II: Placebo + Fulvestrant Placebo Group 2 Interventions

Placebo administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.

Abemaciclib is already approved in United States, European Union for the following indications:

Approved in United States as Verzenio for:

• Hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Approved in European Union as Verzenio for:

• HR+, HER2- advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

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

Findings from Research

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 the MONARCH 2 study, abemaciclib combined with fulvestrant significantly improved progression-free survival (PFS) and overall survival (OS) in patients with hormone receptor positive, HER2-negative advanced breast cancer, showing consistent benefits across both first-line and second-line treatment groups.

The most substantial benefits were seen in patients with primary resistance to endocrine therapy and those with visceral disease, indicating that abemaciclib may be particularly effective for these subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MONARCH 2: Subgroup Analysis of Patients Receiving Abemaciclib Plus Fulvestrant as First-Line and Second-Line Therapy for HR+, HER2--Advanced Breast Cancer. Neven, P., Johnston, SRD., Toi, M., 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]

In the premenopausal subgroup of the MONARCH 2 trial, patients treated with abemaciclib plus fulvestrant experienced significantly improved median progression-free survival (PFS) of 28.6 months compared to 10.26 months for those receiving placebo plus fulvestrant, indicating strong efficacy in hormone receptor-positive, HER2-negative advanced breast cancer.

The safety profile of abemaciclib plus fulvestrant was consistent with previous findings, supporting its use as an effective treatment option for premenopausal patients who are resistant to endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib plus fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in premenopausal women: subgroup analysis from the MONARCH 2 trial. Neven, P., Rugo, HS., Tolaney, SM., et al.[2021]

In the MONARCH 2 study involving 669 women with advanced breast cancer, the combination of abemaciclib and fulvestrant significantly improved progression-free survival (PFS) to a median of 16.4 months compared to 9.3 months with fulvestrant alone.

The combination therapy also achieved a higher objective response rate (ORR) of 48.1% versus 21.3% in the control group, while maintaining a tolerable safety profile, with common side effects including diarrhea and neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MONARCH 2: Abemaciclib in Combination With Fulvestrant in Women With HR+/HER2- Advanced Breast Cancer Who Had Progressed While Receiving Endocrine Therapy. Sledge, GW., Toi, M., Neven, P., et al.[2022]

Abemaciclib is an oral medication that inhibits cyclin-dependent kinases 4 and 6, specifically approved in the USA for treating advanced or metastatic breast cancer that is hormone receptor-positive and HER2-negative.

It is effective both as a combination therapy with fulvestrant for patients who have progressed after endocrine therapy and as a standalone treatment for those who have also undergone chemotherapy, highlighting its role in advanced cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib: First Global Approval. Kim, ES.[2019]

In a pooled analysis of 1152 patients from the MONARCH 2 and MONARCH 3 studies, abemaciclib combined with endocrine therapy showed a consistent improvement in progression-free survival (PFS) across all age groups, indicating its efficacy in treating HR+, HER2- advanced breast cancer regardless of age.

Older patients experienced higher rates of clinically relevant side effects, such as diarrhea and nausea, but these were manageable with dose adjustments, suggesting that while safety concerns exist, the treatment remains effective for older populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of abemaciclib plus endocrine therapy in older patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: an age-specific subgroup analysis of MONARCH 2 and 3 trials. Goetz, MP., Okera, M., Wildiers, H., et al.[2022]

In a phase III study involving 493 postmenopausal women with HR-positive, HER2-negative advanced breast cancer, abemaciclib significantly improved progression-free survival compared to placebo, with a hazard ratio of 0.54, indicating a strong efficacy as initial therapy.

The most common side effect of abemaciclib was diarrhea, occurring in 81.3% of patients, but most cases were mild (grade 1), suggesting that while there are some adverse effects, the treatment has a tolerable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. Goetz, MP., Toi, M., Campone, M., et al.[2022]

Abemaciclib combined with endocrine therapy (ET) significantly improves quality-adjusted life years (QALYs) in patients with high-risk hormone receptor positive, HER2-negative early breast cancer, with an increase of 0.99 QALYs compared to ET alone.

The treatment is considered cost-effective in Italy, with an incremental cost-effectiveness ratio of €22,651 per QALY gained, and a 99% likelihood of being cost-effective at a threshold of €30,000 per QALY.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of abemaciclib with endocrine therapy (ET) versus ET alone for HR+, HER2-, node-positive, high-risk early breast cancer in Italy. Davie, A., Traoré, S., Giovannitti, M., et al.[2023]

References

1. France pubmed.ncbi.nlm.nih.gov

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

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

MONARCH 2: Subgroup Analysis of Patients Receiving Abemaciclib Plus Fulvestrant as First-Line and Second-Line Therapy for HR+, HER2--Advanced Breast Cancer. [2022]

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

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

4. England pubmed.ncbi.nlm.nih.gov

Abemaciclib plus fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in premenopausal women: subgroup analysis from the MONARCH 2 trial. [2021]

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

MONARCH 2: Abemaciclib in Combination With Fulvestrant in Women With HR+/HER2- Advanced Breast Cancer Who Had Progressed While Receiving Endocrine Therapy. [2022]

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

Abemaciclib: First Global Approval. [2019]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and efficacy of abemaciclib plus endocrine therapy in older patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: an age-specific subgroup analysis of MONARCH 2 and 3 trials. [2022]

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

MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. [2022]

9. Italy pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of abemaciclib with endocrine therapy (ET) versus ET alone for HR+, HER2-, node-positive, high-risk early breast cancer in Italy. [2023]