Endocrine Therapy + Abemaciclib for Breast Cancer

Overseen By Jaycee Cushman

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Duke University

Must be taking: Endocrine therapy

Must not be taking: Hormonal birth control

Disqualifiers: Active malignancy, Autoimmune, Immunodeficient, 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: Unknown

Duration: 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of cancer treatments for advanced breast cancer sensitive to estrogen. Researchers aim to understand how these treatments, including abemaciclib (a targeted cancer therapy) and hormone therapies, affect the immune system around tumors. The study includes two groups: one receiving fulvestrant with abemaciclib, and the other receiving an aromatase inhibitor with abemaciclib. Women with advanced breast cancer that has not responded to previous treatments and who have estrogen-receptor positive tumors may be suitable for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for this trial?

The trial does not specify if you need to stop taking your current medications. However, it mentions a 21-day washout period for those who have received chemotherapy before starting the trial. It's best to discuss your specific medications with the trial team.

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

Earlier studies have found the combination of abemaciclib and fulvestrant to be generally safe for patients with advanced breast cancer. Common side effects include diarrhea, tiredness, and nausea, which can usually be managed with medication or dose adjustments.

Research on abemaciclib and aromatase inhibitors (drugs that lower estrogen levels) shows a similar safety profile. Patients often experience mild to moderate side effects like tiredness and diarrhea.

Both treatment combinations have been studied for their safety and have shown promising results. However, anyone considering joining a trial should discuss possible side effects with their doctor. This discussion helps in understanding what to expect and how to manage any issues that might arise. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine abemaciclib, a targeted therapy, with either fulvestrant or aromatase inhibitors, offering a fresh approach to treating breast cancer. Abemaciclib is a CDK4/6 inhibitor that works by stopping cancer cell division, which is different from standard treatments that often rely solely on hormone therapy. By pairing it with fulvestrant, which degrades estrogen receptors, or aromatase inhibitors, which lower estrogen levels, these combinations could enhance effectiveness and potentially overcome resistance seen in traditional therapies. This dual-action approach could provide a more robust defense against tumor growth, sparking hope for improved outcomes in patients.

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

In this trial, participants will receive one of two treatment combinations. Research has shown that combining Fulvestrant with Abemaciclib, one of the combinations being tested, significantly benefits patients with advanced breast cancer. Studies have found that this combination increases the time patients live without their cancer worsening, known as progression-free survival (PFS). Specifically, one study reported a median PFS of 16.9 months, demonstrating a clear benefit over using Fulvestrant alone. For the other combination being tested, an Aromatase Inhibitor with Abemaciclib, evidence indicates that patients lived 12.6 months longer compared to using an Aromatase Inhibitor alone. Both treatment combinations suggest promising results for those with hormone-receptor-positive breast cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Sarah Sammons, MD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

This trial is for women over 18 with advanced ER+/HER2- breast cancer who can swallow pills, have good organ function, and can undergo biopsies. They should not be using hormonal birth control or have active cancers (except certain skin cancers), autoimmune diseases, serious infections, or conditions that make biopsy unsafe.

Inclusion Criteria

My organs are functioning well.

I have a tumor from breast cancer that can be biopsied.

I have fully recovered from any side effects of my recent radiotherapy.

Exclusion Criteria

I do not have serious health issues that would stop me from joining this study.

I am on blood thinners due to a history of blood clots or heart conditions.

I have a bleeding disorder that makes biopsies unsafe for me.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive standard of care endocrine therapy and abemaciclib, with changes in tumor immune microenvironment analyzed

2 years

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Aromatase Inhibitors
• Fulvestrant

Trial Overview The study tests how standard endocrine therapy plus abemaciclib affects immune cells in the tumor environment of breast cancer patients. It involves detailed analysis through single cell RNA sequencing and monitoring changes related to serum estrogen levels.

How Is the Trial Designed?

Group I: Cohort 1 Active Control 2 Interventions

Fulvestrant plus abemaciclib

Group II: Cohort 2 Active Control 2 Interventions

Aromatase inhibitor plus abemaciclib (with or without ovarian suppression)

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?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Published Research Related to This Trial

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 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]

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 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 3 study involving 493 postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer, abemaciclib combined with a nonsteroidal aromatase inhibitor significantly improved progression-free survival (PFS) to 28.18 months compared to 14.76 months for the placebo group.

The objective response rate (ORR) was also higher in the abemaciclib group at 61.0% versus 45.5% in the placebo group, with a tolerable safety profile, although some patients experienced grade ≥3 adverse events like neutropenia and diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer. Johnston, S., Martin, M., Di Leo, A., et al.[2023]

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39754979/

Comparative overall survival of CDK4/6 inhibitors plus an ... This large real-world study suggested that there were no significant OS differences between 1L ribociclib, abemaciclib, and palbociclib in combination with an ...

2. verzenio.lilly.com verzenio.lilly.com/hcp/efficacy-mbc/aromatase-inhibitor-trial-design

Verzenio® + AI (aromatase inhibitor) | Efficacy - Eli Lilly Verzenio + AI improved median PFS by 14.3 months at the 8-year analysis. 5 Verzenio reduced risk of progression or death by 46.5% in the ITT population.

3. esmoopen.com esmoopen.com/article/S2059-7029(25)01439-5/fulltext

Real-world progression-free survival of CDK4/6 inhibitors ... Real-world study of overall survival with palbociclib plus aromatase inhibitor in HR+/HER2− metastatic breast cancer. NPJ Breast Cancer.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0960977625006149

Metastatic Breast Cancer: A Propensity-Matched ... (2025) found no significant overall survival differences between abemaciclib and palbociclib when combined with aromatase inhibitors (adjusted ...

5. breastcancer.org breastcancer.org/research-news/verzenio-plus-aromatase-inhibitor-improves-survival-in-advanced-stage-hormone-receptor-positive-her2-negative-breast-cancer

Verzenio Plus Aromatase Inhibitor Improves Survival in ... The latest results from the MONARCH 3 study show that adding Verzenio to an aromatase inhibitor improves overall survival by 12.6 months.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38729566/

advanced breast cancer: final overall survival results of ... Conclusions: Abemaciclib combined with an NSAI resulted in clinically meaningful improvement in median OS (intent-to-treat population: 13.1 ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02763566

NCT02763566 | A Study of Abemaciclib (LY2835219) in ... The main purpose of this study is to evaluate the efficacy of the study drug abemaciclib in postmenopausal women with hormone receptor-positive (HR+), human ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S1526820925001168

Clinical Breast Cancer The phase 2 HERMIONE-7 trial aims to evaluate the efficacy and safety of Abemaciclib + AIs in HR+/ HER2− MBC patients who have received Fulvestrant alone as ...

9. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-025-14194-w

Efficacy and safety of first-line CDK4/6 inhibitors plus AI ... Abemaciclib plus AI ranked at the top for prolonging PFS in majority of the subgroups (patients with baseline ECOG of 1 75.0%, those aged < 65 ...

10. ascopubs.org ascopubs.org/doi/pdf/10.1200/EDBK-25-473384

Side Effects of New and Emerging Breast Cancer Therapies This review provides a comprehensive description of the toxicities of these novel and emerging breast cancer therapies and outlines effective.