Abemaciclib + SRS for Breast Cancer Brain Metastases

Overseen By Kamran A Ahmed, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must be taking: Endocrine therapy

Must not be taking: Abemaciclib

Disqualifiers: Leptomeningeal disease, Whole brain radiation, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

31 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a single arm study of abemaciclib and endocrine therapy with stereotactic radiosurgery (SRS) among patients with hormone receptor (HR)+/HER2- metastatic breast cancer brain metastases.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the drug Abemaciclib for treating breast cancer brain metastases?

Research shows that Abemaciclib, when combined with endocrine therapy, significantly improves progression-free survival in patients with advanced hormone receptor-positive, HER2-negative breast cancer. This suggests it may be effective in managing breast cancer brain metastases as well. ^{1 2 3 4 5}

Is Abemaciclib safe for use in humans?

Abemaciclib, when used in combination with endocrine therapy for breast cancer, has shown a tolerable safety profile in clinical trials. Common side effects include diarrhea, infections, and neutropenia (low white blood cell count), but these are generally manageable. ^{1 2 3 4 6}

What makes the drug Abemaciclib unique for treating breast cancer brain metastases?

Abemaciclib is unique because it is a CDK4/6 inhibitor that, when combined with endocrine therapy, has shown effectiveness in treating hormone receptor-positive breast cancer with brain metastases, a condition that typically has a poor prognosis and limited treatment options. This combination has demonstrated the ability to achieve partial remission in brain metastases, offering a novel approach compared to traditional therapies. ^{1 2 3 7 8}

Research Team

Kamran A Ahmed, MD

Principal Investigator

Moffitt Cancer Center

Heather Han, MD

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

This trial is for individuals with HR+/HER2- metastatic breast cancer brain metastases. Participants can have had prior radiation treatments if there's measurable disease not previously treated with radiation. They must be able to undergo stereotactic radiosurgery, have ≤ 15 brain lesions eligible for this treatment, and a performance status of 0 to 2. Women must test negative for pregnancy and agree to use contraception.

Inclusion Criteria

I can take care of myself and am up and about more than half of my waking hours.

If you can have babies, you need to have a negative pregnancy test within 7 days before starting the medicine abemaciclib.

I have a brain tumor or cavity from surgery that can be measured and is at least 0.5 cm big.

Exclusion Criteria

I am not pregnant or breastfeeding.

Prisoners or individuals who are involuntarily incarcerated

I haven't had any other cancer besides this one in the last 2 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase I

One week of abemaciclib followed by stereotactic radiation to sites of brain metastases or post-operative cavities with continued abemaciclib. Safety monitored by a 3+3 design.

1-2 weeks

Treatment Phase II

Continuation of abemaciclib and stereotactic radiation at the phase 1 dose to sites of brain metastases or post-operative cavities.

Up to 12 months

Follow-up

Participants are monitored for intracranial progression free survival and other outcomes.

Up to 12 months

Treatment Details

Interventions

• Abemaciclib
• Endocrine therapy
• Stereotactic Radiosurgery (SRS)

Trial Overview The study tests the combination of abemaciclib and endocrine therapy alongside stereotactic radiosurgery (SRS) in patients with specific breast cancer that has spread to the brain. It's a single-arm study, meaning all participants receive the same treatment without comparison groups.

Participant Groups

Group I: Phase 2: Radiation Therapy and Abemaciclib Experimental Treatment 3 Interventions

Treatment will be initiated with one week of abemaciclib followed by stereotactic radiation at the phase 1 dose to sites of brain metastases or post-operative cavities with continued abemaciclib.

Group II: Phase 1: Radiation Therapy and Abemaciclib Experimental Treatment 3 Interventions

Treatment will be initiated with one week of abemaciclib followed by stereotactic radiation to sites of brain metastases or post-operative cavities with continued abemaciclib. In the phase I portion, safety will be monitored initially by a 3+3 design. If unexpected neurologic toxicities are noted, the dose of radiation therapy will be modified.

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?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

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

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]

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 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 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]

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]

A patient with hormone receptor-positive breast cancer and cystic brain metastases (CBM) showed partial remission after treatment with abemaciclib and fulvestrant, indicating potential efficacy of this combination therapy for CBM.

Despite the positive response in CBM, the patient continued to experience an increase in extracranial bone metastases, highlighting the complexity of treating metastatic breast cancer and the need for ongoing monitoring and treatment adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib plus fulvestrant for the treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer with cystic brain metastases: A case report and literature review. Chu, Z.[2022]

In a phase II study involving patients with hormone receptor-positive metastatic breast cancer and brain or leptomeningeal metastases, abemaciclib showed an intracranial clinical benefit rate of 24% in cohort A (n=58), indicating some effectiveness in this heavily pretreated group.

Abemaciclib achieved significantly high concentrations in brain metastases tissue, exceeding the levels needed for effective inhibition of CDK4 and CDK6, suggesting potential for further exploration of this treatment in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Study of Abemaciclib in Patients with Brain Metastases Secondary to Hormone Receptor-Positive Breast Cancer. Tolaney, SM., Sahebjam, S., Le Rhun, E., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

First-Line Abemaciclib Effective in ER+ Breast Cancer. [2019]

2. France pubmed.ncbi.nlm.nih.gov

Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence. [2023]

3. 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]

4. United States pubmed.ncbi.nlm.nih.gov

MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. [2022]

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

Abemaciclib: First Global Approval. [2019]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Abemaciclib plus fulvestrant for the treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer with cystic brain metastases: A case report and literature review. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

A Phase II Study of Abemaciclib in Patients with Brain Metastases Secondary to Hormone Receptor-Positive Breast Cancer. [2021]