Abemaciclib for Older Patients with Breast Cancer

Recruiting at 2 trial locations

Overseen By Joanne Mortimer, MD

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: Immune-suppressive, Herbal medications

Disqualifiers: Major surgery, Active infections, GI impairment, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: Up to 6 cycles (24 weeks)

43 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how abemaciclib, a cancer medication, affects older adults with breast cancer that has spread to other parts of the body. The focus is on hormone receptor-positive and HER2-negative breast cancer, a type that doesn’t respond to certain common treatments. Participants should be 70 or older, have breast cancer that has worsened after previous treatments, and must not have any severe uncontrolled health issues. The study aims to determine if abemaciclib can be an effective treatment option for this group. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as other investigational therapies, anticancer agents not part of the study, immune-suppressive agents, and herbal medications, at least 7 days before starting the study drug. It's best to discuss your current medications with the trial team to see if any need to be stopped.

Is there any evidence suggesting that abemaciclib is likely to be safe for older patients with breast cancer?

Research has shown that abemaciclib, the treatment under study in this trial, is generally safe. In earlier studies with patients who had early breast cancer, researchers found the side effects of abemaciclib to be manageable and reversible. Most people can tolerate the treatment well. Although abemaciclib has helped some breast cancer patients live longer, all treatments can have side effects. Participants in trials like this contribute to understanding the treatment's safety across different groups, especially older adults. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard chemotherapy and hormone therapy options for older patients with breast cancer, Abemaciclib is unique because it specifically targets proteins called CDK4 and CDK6. These proteins are involved in cell division, and by inhibiting them, Abemaciclib can potentially slow down or stop the growth of cancer cells. Researchers are excited about this treatment because it offers a targeted approach, which may lead to fewer side effects and improved quality of life compared to traditional treatments. Additionally, Abemaciclib is taken orally, which can be more convenient for patients compared to intravenous therapies.

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

Research shows that abemaciclib may help treat hormone receptor-positive (HR+) and HER2-negative breast cancer. Studies have found that abemaciclib, particularly when combined with other treatments, can significantly improve survival rates. For example, it reduced the risk of death by 15.8% compared to standard hormone therapy alone. Additionally, in everyday medical practice, patients using abemaciclib experienced better survival outcomes. These findings suggest that abemaciclib could be a good option for older patients with metastatic breast cancer. ^{3 5 6 7 8}

Who Is on the Research Team?

Joanne E Mortimer, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for patients aged 70 or older with hormone receptor positive, HER2 negative metastatic breast cancer who have progressed on prior treatments. They must have recovered from previous therapies' side effects and not have certain infections, severe medical conditions, or a history of non-compliance to medical regimens.

Inclusion Criteria

Your platelet count is at least 100 billion per liter.

My cancer can be measured by tests or seen on scans.

I can read and understand either English or Spanish.

Exclusion Criteria

History of non-compliance to medical regimen

I am not taking any medications that are not allowed in the study.

I have a digestive issue that affects how I absorb medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive abemaciclib orally twice daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 6 cycles (24 weeks)

Monthly visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib

Trial Overview The study tests the safety of abemaciclib monotherapy in elderly patients with advanced breast cancer. It's a phase IIa trial focusing on those who've had other treatments before. Participants will also complete questionnaires as part of the study.

How Is the Trial Designed?

Group I: Treatment (abemaciclib) Experimental Treatment 2 Interventions

Patients receive abemaciclib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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 study involving 5632 patients with early breast cancer, abemaciclib combined with endocrine therapy significantly improved invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in premenopausal patients, showing a 42.2% and 40.3% reduction in risk, respectively.

The safety profile of abemaciclib in premenopausal patients was consistent with the overall safety data, indicating that it is a safe and effective treatment option for this subgroup of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety results by menopausal status in monarchE: adjuvant abemaciclib combined with endocrine therapy in patients with HR+, HER2-, node-positive, high-risk early breast cancer. Paluch-Shimon, S., Neven, P., Huober, J., et al.[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 phase III clinical trials (MONARCH 2 and MONARCH 3), abemaciclib, a CDK4 & 6 inhibitor, significantly improved progression-free survival and overall survival in women with hormone receptor positive (HR+) and HER2-negative advanced breast cancer when used in combination with endocrine therapy.

Abemaciclib demonstrated a tolerable safety profile, making it a promising treatment option for patients who have progressed after previous endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Development of CDK4 & 6 Inhibitor Abemaciclib in Breast Cancer]. Masuda, N., Saji, S., Kawaguchi, T., et al.[2021]

Abemaciclib is a potent oral CDK4 and CDK6 inhibitor that effectively treats hormone receptor-positive, HER2-negative advanced or metastatic breast cancer, showing response rates between 19.7% and 59% in major clinical trials.

The drug is well-tolerated, with common side effects including diarrhea and neutropenia, and it offers the advantage of continuous dosing and potential use as a monotherapy, making it a promising option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib: The Newest CDK4/6 Inhibitor for the Treatment of Breast Cancer. Palumbo, A., Lau, G., Saraceni, M.[2020]

A new ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to effectively monitor abemaciclib levels in patients with advanced breast cancer, showing high accuracy and precision in quantification.

This method allows for robust therapeutic drug monitoring (TDM) of abemaciclib, which can help personalize treatment and improve adherence in patients, addressing challenges in the emerging field of oral antitumor therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An UHPLC-MS/MS method for quantification of the CDK4/6 inhibitor abemaciclib in human serum. Habler, K., Vogeser, M., Teupser, D.[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]

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 study of 1474 early breast cancer patients, 76.1% had the HR+/Her2- subtype, but only 19.4% met the criteria for adjuvant treatment with abemaciclib, indicating a limited but significant patient population that could benefit from this therapy.

Almost half (48.9%) of the eligible patients did not receive prior chemotherapy, suggesting that in real-world settings, fewer patients may be pretreated compared to clinical trials, highlighting the need for tailored care strategies to manage the therapy's monitoring requirements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of Adjuvant Treatment with Abemaciclib-Real-World Data from a Large German Breast Center. Dannehl, D., Volmer, LL., Weiss, M., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41092644/

metastatic breast cancer: A propensity-matched ... Conclusions: In this large, real-world cohort study, first-line abemaciclib was associated with a significant overall survival benefit compared ...

2. prnewswire.com prnewswire.com/news-releases/lillys-verzenio-abemaciclib-prolonged-survival-in-hr-her2--high-risk-early-breast-cancer-with-two-years-of-treatment-302586849.html

Lilly's Verzenio® (abemaciclib) prolonged survival in HR+, ... Verzenio is the first contemporary therapy in over two decades to demonstrate a significant overall survival benefit in adjuvant HR+, HER2−, ...

3. 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 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04031885

NCT04031885 | A Study of Abemaciclib (LY2835219) in ... The reason for this study is to compare the efficacy of abemaciclib, in combination with fulvestrant, to that of physician's choice of chemotherapy in women ...

5. appliedclinicaltrialsonline.com appliedclinicaltrialsonline.com/view/verzenio-kisqali-positive-long-term-results-early-breast-cancer-trials

Verzenio and Kisqali Deliver Positive Long-Term Results ... Topline findings · Verzenio plus endocrine therapy reduced the risk of death by 15.8% versus ET alone in high-risk HR+/HER2– early breast cancer.

6. sciencedirect.com sciencedirect.com/science/article/pii/S0923753425049488

Overall Survival with Abemaciclib in Early Breast Cancer Patient reported outcomes findings confirm a tolerable and reversible toxicity profile. The long-term safety data compiled did not support any ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03155997

Study Details | NCT03155997 | Endocrine Therapy With or ... The purpose of this study is to evaluate the safety and efficacy of the study drug abemaciclib in participants with high risk, node positive, early stage, ...

8. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK609559/

Abemaciclib (Verzenio) - NCBI Bookshelf - NIH In patients with HR-positive, HER2-negative early-stage breast cancer, the 5-year survival rate is greater than 90%. Although patients with early-stage breast ...