Fulvestrant + Abemaciclib for Breast Cancer

Overseen By Jenny C Chang, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

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

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: 2

Duration: Until disease progression or unacceptable toxicity

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if pausing a certain medication can enhance breast cancer treatment effectiveness. It examines the use of fulvestrant (a hormone therapy) and abemaciclib (a targeted therapy) for individuals with ER-positive, HER2-negative metastatic breast cancer who have experienced disease progression despite previous treatments. Participants must have this type of breast cancer, have undergone similar treatments, and not have active or untreated brain conditions. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group.

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.

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

Research has shown that the combination of abemaciclib and fulvestrant is well-studied for treating advanced breast cancer. In these studies, patients using this combination experienced significant benefits.

Regarding safety, abemaciclib and fulvestrant together are generally well-tolerated. While some side effects occur, they are usually manageable. Common side effects include fatigue, diarrhea, and nausea, but these are often mild.

Overall, previous research suggests this treatment combination is safe for many patients. However, individual experiences may vary, so discussing any concerns with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for breast cancer?

Researchers are excited about the combination of Fulvestrant and Abemaciclib for breast cancer because it targets the disease in a unique way. Fulvestrant works by blocking estrogen receptors, which is critical since many breast cancers rely on estrogen to grow. Abemaciclib, on the other hand, inhibits proteins called CDK4 and CDK6, which are vital for cancer cell division. This dual approach not only attacks the cancer cells' ability to use estrogen but also hampers their ability to multiply, offering a potentially more effective treatment than standard hormone therapies.

What evidence suggests that this treatment might be an effective treatment for breast cancer?

Research has shown that combining abemaciclib with fulvestrant can significantly improve outcomes for patients with certain types of breast cancer. In this trial, participants will receive both fulvestrant and abemaciclib. Studies have found that this combination helps patients live longer without their cancer worsening, compared to those taking fulvestrant alone. Specifically, one study found that nearly half of the patients (48.1%) responded well to this combination, more than doubling the response rate of fulvestrant alone. Additionally, adding abemaciclib can extend life by about nine months in some cases. These findings suggest that this combination is a promising treatment for advanced-stage, hormone-receptor-positive breast cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Polly Niravath, MD

Principal Investigator

The Methodist Hospital Research Institute

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Fulvestrant

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.

How Is the Trial Designed?

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

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?

The Methodist Hospital Research Institute

Lead Sponsor

Trials

299

Recruited

82,500+

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

Published Research Related to This Trial

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 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, 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]

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]

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, 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]

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]

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]

Citations

1. onclive.com onclive.com/view/abemaciclib-fulvestrant-boosts-pfs-in-hr-her2-breast-cancer-post-cdk4-6i-progression

Abemaciclib/Fulvestrant Boosts PFS in HR+/HER2 The addition of abemaciclib (Verzenio) to fulvestrant (Faslodex) led to a significant improvement in progression-free survival (PFS) vs fulvestrant alone.

2. breastcancer.org breastcancer.org/research-news/verzenio-plus-faslodex-improves-overall-survival

Adding Verzenio to Faslodex Improves Overall Survival Study results show adding Verzenio to Faslodex improves overall survival by nine months for advanced-stage, hormone-receptor-positive, ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28580882/

MONARCH 2: Abemaciclib in Combination With ... In patients with measurable disease, abemaciclib plus fulvestrant achieved an ORR of 48.1% (95% CI, 42.6% to 53.6%) compared with 21.3% (95% CI, ...

4. verzenio.lilly.com verzenio.lilly.com/hcp/efficacy-mbc/plus-fulvestrant

Verzenio® + Fulvestrant | Efficacy - Eli Lilly Verzenio plus fulvestrant improved OS in the ITT population, with consistent results even in patients at higher risk · OS in patients with visceral disease · OS ...

5. lbbc.org lbbc.org/news/abemaciclib-shows-small-benefit-after-a-prior-cdk-4-6-inhibitor-stops-working-asco-2024

Abemaciclib shows small benefit after a prior CDK 4/6 ... Participants in the abemaciclib-plus-fulvestrant group went six months without cancer progressing compared to 5.3 months for those in the fulvestrant-only group ...

6. ascopubs.org ascopubs.org/doi/10.1200/OA-25-00052

Final Overall Survival Results From MONARCH 2 Consistent with the primary analysis, abemaciclib plus fulvestrant showed persistent PFS benefit at the final analysis. The median PFS was 16.9 ...

7. onclive.com onclive.com/view/abemaciclib-fulvestrant-improves-pfs-across-hr-her2-advanced-breast-cancer-subgroups

Abemaciclib/Fulvestrant Improves PFS Across HR+/HER2 In patients who had received CDK4/6 inhibition for less than 18 months, the median PFS with abemaciclib plus fulvestrant (n = 89) was 5.6 months ...

8. curetoday.com curetoday.com/view/verzenio-combo-may-improve-survival-in-hr-her2-advanced-breast-cancer

Verzenio Combo May Improve Survival in HR+/HER2 Verzenio plus Faslodex improved PFS in HR+, HER2– advanced breast cancer post-CDK4/6i progression, reducing progression or death risk by 27%.

9. oncpracticemanagement.com oncpracticemanagement.com/special-issues/the-evolution-of-abemaciclib-clinical-trial-data-for-the-treatment-of-hr-positive-her2-negative-metastatic-breast-cancer

The Evolution of Abemaciclib Clinical Trial Data for ... PFS was significantly improved with the combination of abemaciclib plus fulvestrant of 16.9 months compared with 9.3 months with fulvestrant (hazard ratio, ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7990838/

Safety and efficacy of abemaciclib plus endocrine therapy ... Abemaciclib in combination with endocrine therapy (ET) has demonstrated significant efficacy benefits in HR+ , HER2− advanced breast cancer patients.