Aromatase Inhibitors + Abemaciclib for Breast Cancer

(MONARCH 3 Trial)

Not currently recruiting at 345 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Must be taking: Nonsteroidal aromatase inhibitors

Must not be taking: Endocrine therapy, Chemotherapy

Disqualifiers: Visceral crisis, CNS metastasis, others

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: Unknown

Duration: Up to 32 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of combining nonsteroidal aromatase inhibitors (NSAI) with abemaciclib, a targeted cancer therapy, for postmenopausal women with specific breast cancer types. Participants will receive either abemaciclib or a placebo, alongside standard treatments like anastrozole or letrozole. The trial aims to determine if this combination can manage breast cancer that has spread or cannot be treated with surgery. Women with hormone receptor-positive (HR+), HER2-negative breast cancer who have experienced disease recurrence or metastasis may be suitable for this trial. As a Phase 3 trial, it represents the final step before potential FDA approval, offering participants a chance to contribute to a treatment that could soon become widely available.

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 participate if you are currently receiving certain treatments like chemotherapy for breast cancer or investigational drugs. 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?

Research has shown that abemaciclib, when combined with drugs like anastrozole or letrozole, is generally well-tolerated. In studies involving patients with advanced breast cancer, abemaciclib was tested alongside these hormone therapies. Patients managed the combination well, suggesting it can be a safe option.

Some patients experienced side effects, but these were often manageable. Common side effects included diarrhea and fatigue. However, many patients reported significant benefits from using abemaciclib with hormone therapy.

Abemaciclib is already approved for treating certain types of breast cancer, indicating its relative safety for humans. It is important to consult healthcare providers to understand the potential risks and benefits for individual health situations. ^{1 2 3 4 5}

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

Researchers are excited about the combination of Aromatase Inhibitors with Abemaciclib for breast cancer because it offers a novel approach by integrating a CDK4/6 inhibitor with standard hormone therapies like Anastrozole and Letrozole. While traditional treatments primarily focus on reducing estrogen production to slow cancer growth, Abemaciclib works differently by specifically targeting proteins (CDK4 and 6) that cancer cells need to divide and grow. This combined approach not only aims to enhance the effectiveness of hormone therapies but also potentially delays disease progression, offering hope for improved outcomes in patients with hormone receptor-positive breast cancer.

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

In this trial, participants will receive either Abemaciclib combined with nonsteroidal aromatase inhibitors (NSAIs) like anastrozole or letrozole, or a placebo combined with NSAIs. Studies have shown that adding Abemaciclib to NSAIs can significantly benefit women with breast cancer. One study found that using Abemaciclib with hormone therapy extended the time before cancer returned. Another study showed that combining Abemaciclib with an aromatase inhibitor increased survival by over a year for women with advanced-stage hormone receptor-positive breast cancer. These findings suggest that Abemaciclib, when used with NSAIs, effectively improves survival and delays cancer recurrence. ^{6 7 8 9 10}

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 postmenopausal women with hormone receptor-positive, HER2-negative breast cancer who can swallow capsules and have either measurable disease or bone-only disease. They should not have received certain prior treatments like everolimus or chemotherapy for advanced breast cancer, nor should they have central nervous system metastasis or be in another conflicting study.

Inclusion Criteria

I am fully active and can carry on all pre-disease activities without restriction.

I've stopped and recovered from radiotherapy aimed at easing symptoms or preventing bone fractures.

My breast cancer is hormone receptor-positive and HER2-negative.

Exclusion Criteria

Are currently receiving an investigational drug in a clinical trial or participating in any other type of medical research judged not to be scientifically or medically compatible with this study

I haven't taken any unapproved drugs within the last 14 or 21 days, depending on the drug type.

I started treatment with bisphosphonates or RANK-L inhibitors less than a week ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 150 mg Abemaciclib or placebo orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28-day cycles

Up to 32 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Anastrozole
• Letrozole

Trial Overview The effectiveness of nonsteroidal aromatase inhibitors (like Anastrozole and Letrozole) combined with Abemaciclib versus a placebo is being tested. Participants will randomly receive either the drug combination or a placebo at a ratio of 2:1.

How Is the Trial Designed?

Group I: Abemaciclib + NSAI Experimental Treatment 3 Interventions

150 milligrams (mg) Abemaciclib orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).

Group II: Placebo + NSAI Placebo Group 3 Interventions

Placebo orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).

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

Published Research Related to This Trial

In a study using a breast tumor model with ovariectomized mice, letrozole was found to significantly extend the time for tumor progression compared to tamoxifen alone or in combination with letrozole, with letrozole alone allowing tumors to double in size after 34 weeks versus 16 weeks for tamoxifen.

Tumors that progressed while on tamoxifen remained sensitive to second-line treatment with letrozole, indicating a potential treatment pathway, while tumors progressing on letrozole did not respond to subsequent antiestrogen therapies, highlighting the need for further research on effective second-line options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic strategies using the aromatase inhibitor letrozole and tamoxifen in a breast cancer model. Long, BJ., Jelovac, D., Handratta, V., et al.[2022]

In a study involving 3697 postmenopausal women with hormone receptor-positive early breast cancer, the upfront treatment with aromatase inhibitors for 5 years did not show superior disease-free survival compared to a switch strategy of 2 years of tamoxifen followed by 3 years of aromatase inhibitors, with 5-year disease-free survival rates of 89.8% and 88.5%, respectively.

No significant differences in efficacy were found among the three aromatase inhibitors (anastrozole, exemestane, and letrozole), suggesting that factors like patient preference and tolerability should guide treatment decisions rather than efficacy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial. De Placido, S., Gallo, C., De Laurentiis, M., et al.[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]

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]

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]

Three new third-generation aromatase inhibitors (anastrozole, letrozole, and vorozole) have shown superior efficacy and tolerability compared to previous treatments for post-menopausal women with metastatic breast cancer after tamoxifen therapy, based on phase III trials.

Letrozole is significantly more effective than megestrol acetate, while all three inhibitors are better tolerated than progestin treatments, particularly regarding weight gain, marking a clear advancement in second-line hormonal therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The third-generation non-steroidal aromatase inhibitors: a review of their clinical benefits in the second-line hormonal treatment of advanced breast cancer. Hamilton, A., Piccart, M.[2020]

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]

Anastrozole and letrozole are effective oral treatments for advanced breast cancer in postmenopausal women, especially when other therapies like tamoxifen have not worked.

Both drugs are claimed to be more effective and less toxic than the standard treatment, megestrol acetate, although the review assesses the validity of these claims.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New aromatase inhibitors for breast cancer. [2019]

Citations

1. 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 ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.01994

Results From a Preplanned monarchE Overall Survival ... Two years of adjuvant abemaciclib combined with endocrine therapy (ET) resulted in a significant improvement in invasive disease-free survival (IDFS) and ...

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

Verzenio® + ET for Early Breast Cancer | Efficacy - Eli Lilly At the 4-year IDFS analysis (median follow-up of 42 months), 85.5% of patients remained recurrence free with Verzenio + ET vs 78.6% with ET alone (HR=0.65 [95% ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03988114

A Study of Abemaciclib (LY2835219) in Participants With ... The reason for this study is to see if the drug abemaciclib in combination with nonsteroidal aromatase inhibitors (anastrozole or letrozole) is effective in ...

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. 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.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02057133

NCT02057133 | A Study of LY2835219 (Abemaciclib) in ... This study evaluates the safety of abemaciclib in combination therapies (letrozole, anastrozole, tamoxifen, exemestane, exemestane plus everolimus, ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/208716s017lbl.pdf

VERZENIO® (abemaciclib) tablets, for oral use The data described below reflect exposure to VERZENIO in 441 patients with. HR-positive, HER2-negative advanced breast cancer who received at least one dose of ...

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

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 ...

10. tandfonline.com tandfonline.com/doi/full/10.1080/14796694.2025.2558280

Real-world treatment outcomes of abemaciclib in older ... Among these, 1,681 (45.4%) were older patients (≥65 years old) with 30.5% aged 65–69 years, 35.8% aged 70–74 years, and 33.7% aged ≥75 years, respectively.