Fulvestrant + Abemaciclib for Breast Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Polly Niravath, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: The Methodist Hospital Research Institute

Must be taking: GnRH agonists

Must not be taking: CYP3A inhibitors, anticoagulants

Disqualifiers: Active malignancy, uncontrolled conditions, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

The study will investigate if CDK4/6 inhibitor holiday will reset the cell cycle process to respond to the combination of fulvestrant and abemaciclib, and this approach may represent an effective therapeutic strategy to manage such patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use strong cytochrome P450 (CYP)3A inhibitors or inducers. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

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

Research shows that combining Abemaciclib with Fulvestrant significantly improves progression-free survival and overall survival in patients with hormone receptor-positive, HER2-negative advanced breast cancer compared to Fulvestrant alone. ^{1 2 3 4 5}

Is the combination of Fulvestrant and Abemaciclib safe for humans?

The combination of Fulvestrant and Abemaciclib has been studied in patients with advanced breast cancer, showing an acceptable safety profile. Common side effects include diarrhea, infections, and neutropenia (low white blood cell count), which were manageable. ^{1 2 4 6 7}

How is the drug combination of Fulvestrant and Abemaciclib unique for breast cancer treatment?

The combination of Fulvestrant and Abemaciclib is unique because it targets hormone receptor-positive, HER2-negative advanced breast cancer by using Abemaciclib, a CDK4/6 inhibitor, to enhance the effects of Fulvestrant, an endocrine therapy. This combination has been shown to significantly extend progression-free survival compared to Fulvestrant alone, offering a valuable option for patients who have progressed on previous endocrine therapies. ^{1 4 5 6 8}

Research Team

Polly Niravath, MD

Principal Investigator

The Methodist Hospital Research Institute

Eligibility Criteria

This trial is for postmenopausal women over 18 with ER-positive, HER2-negative metastatic breast cancer that has worsened on a CDK4/6 inhibitor and an AI. Participants must be able to take oral meds, have no severe heart conditions or mental health issues affecting participation, not be pregnant or breastfeeding, and agree to use contraception during the trial.

Inclusion Criteria

My blood, liver, and kidney functions are all within normal ranges.

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

Willingness to use an adequate method of contraception for the course of the trial through 1 year after the last dose of trial treatment

Exclusion Criteria

You are allergic to certain medications or their ingredients.

Currently participating in another study involving investigational therapy

I have a bleeding disorder or am currently using blood thinners.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Fulvestrant Run-In

Participants receive fulvestrant at a dose of 500 mg intramuscularly on Days 1 and 15 of the 28-day run-in period

4 weeks

2 visits (in-person)

Treatment

Participants receive fulvestrant plus abemaciclib in 28-day cycles until disease progression or unacceptable toxicity

Until disease progression or unacceptable toxicity

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Abemaciclib (CDK4/6 Inhibitor)
• Fulvestrant (Hormone Therapy)

Trial Overview The study tests if taking a one-month break from abemaciclib can make the body more responsive to it when used with fulvestrant afterward. Some participants will start directly on both drugs while others will have a run-in period with just fulvestrant before adding abemaciclib.

Participant Groups

Group I: Fulvestrant plus Abemaciclib Arm with Fulvestrant Run-In Experimental Treatment 1 Intervention

A 1-month (28 days) run-in of fulvestrant will precede fulvestrant plus abemaciclib treatment. Fulvestrant at a dose of 500 mg will be administered intramuscularly (IM) into the buttocks slowly (1-2 minutes per injection) as two 5-mL injections, one in each buttock, on Days 1 and 15 of the run-in period. After the fulvestrant run-in, fulvestrant plus abemaciclib will be administered in 28-day cycles until disease progression or unacceptable toxicity. Fulvestrant (500 mg IM) will be administered on Day 1 of each 28-day cycle. Abemaciclib at a dose of 150 mg will be given p.o. BID on Days 1-28 of each cycle

Who Is Running the Clinical Trial?

The Methodist Hospital Research Institute

Lead Sponsor

Trials

299

Recruited

82,500+

Dr. John P. Cooke

The Methodist Hospital Research Institute

Chief Medical Officer since 2013

MD, PhD

Dr. Jenny Chang

The Methodist Hospital Research Institute

Chief Executive Officer

MBBChir from University of Cambridge, MHCM from Johns Hopkins University

Eli Lilly and Company

Industry 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]

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]

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]

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. 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]

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

Abemaciclib: First Global Approval. [2019]

8. 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]