Combination Therapy for Advanced Breast Cancer

Overseen By Chao Family Comprehensive Cancer Center University of California, Irvine

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, Irvine

Must not be taking: Fulvestrant

Disqualifiers: HER2 positive, Triple negative, Inflammatory, others

Stay on Your Current Meds You can continue your current medications while participating

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: 3 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of a combination of three drugs—anastrozole, fulvestrant, and abemaciclib (Verzenio)—in treating advanced hormone receptor-positive breast cancer. It targets patients newly diagnosed with advanced or metastatic breast cancer or those whose cancer has returned after being treatment-free for over a year. Suitable candidates have hormone receptor-positive breast cancer that has spread or recurred after a long treatment break. Participants should not have HER2-positive or triple-negative breast cancer and should not have undergone recent chemotherapy or radiotherapy. As a Phase 2 trial, this study measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important research.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you have had chemotherapy or radiotherapy within the last 12 months, you may not be eligible. 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 shows that combining abemaciclib, anastrozole, and fulvestrant is promising for safely treating certain breast cancers. Studies have found that abemaciclib, when paired with other hormone therapies, provides benefits without causing severe side effects for most people.

Additionally, using fulvestrant and anastrozole together has been linked to longer survival times in patients, indicating it is generally well-tolerated. While all medications can have side effects, evidence suggests that this combination is manageable for many patients.

For those considering joining a trial, it's important to know that this treatment has been tested in other settings and found to be generally safe. Always discuss any concerns with a doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination therapy of Fulvestrant, Anastrozole, and Abemaciclib for advanced breast cancer because it uniquely combines targeted therapy with hormone therapy. While standard treatments often focus solely on hormone blockade, this regimen includes Abemaciclib, a CDK4/6 inhibitor, which disrupts cancer cell division and growth. This multi-faceted approach has the potential to enhance treatment effectiveness by simultaneously targeting different pathways that cancer cells use to proliferate. Additionally, the inclusion of Abemaciclib offers a novel mechanism of action that could improve outcomes in patients who may not respond well to traditional hormone therapies alone.

What evidence suggests that this combination therapy could be effective for advanced breast cancer?

This trial will evaluate the combination of Fulvestrant, Anastrozole, and Abemaciclib for advanced breast cancer. Research has shown that using Fulvestrant and Anastrozole together can extend the lives of people with advanced breast cancer. Specifically, studies have found that Fulvestrant is more effective than Anastrozole alone in slowing cancer progression. Additionally, Abemaciclib, when combined with hormone therapy, significantly improved survival for patients with hormone receptor-positive breast cancer. These treatments work together to target cancer cells more effectively, offering hope for better outcomes. ^{1 3 4 6 7}

Who Is on the Research Team?

Rita S. Mehta

Principal Investigator

Chao Family Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for post-menopausal women with HR+HER2- advanced or metastatic breast cancer, who have relapsed more than a year after prior treatments. Participants must be over 18, in good health with proper organ function, and not currently pregnant. They should agree to contraception if of child-bearing potential.

Inclusion Criteria

My cancer returned more than a year after completing initial treatment, with no treatment for advanced stages.

My organs and bone marrow are working well.

I am post-menopausal.

Exclusion Criteria

My breast cancer is HER2 positive or triple negative.

I have been diagnosed with inflammatory breast cancer.

I have had chemotherapy or radiotherapy within the last year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive combination therapy with anastrozole, fulvestrant, and abemaciclib

3 months

Fulvestrant: Initial 2 visits (in-person), Maintenance: 1 visit monthly (in-person); Anastrozole and Abemaciclib: daily oral administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Anastrozole
• Fulvestrant

Trial Overview The study tests a combination therapy using Anastrazole, Fulvestrant & Abemaciclib on patients newly diagnosed with advanced breast cancer or those whose cancer returned after treatment-free interval of over 12 months.

How Is the Trial Designed?

Group I: Fulvestrant + Anastrozole + Abemaciclib Experimental Treatment 3 Interventions

Fulvestrant, intramuscular, Initial: 500 mg on days 1 and 15; Maintenance: 500 mg once monthly. Anastrozole, oral, 1mg tablet daily Abemaciclib 150 mg twice daily

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?

University of California, Irvine

Lead Sponsor

Trials

580

Recruited

4,943,000+

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]

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 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 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]

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 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 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 neoMONARCH study, postmenopausal women with HR+/HER2- breast cancer showed significant decreases in Ki67 expression and achieved higher rates of complete cell-cycle arrest when treated with abemaciclib alone or in combination with anastrozole compared to anastrozole alone.

The combination therapy not only inhibited cancer cell growth but also enhanced immune activation, suggesting a dual mechanism of action that could improve treatment outcomes, while the most common side effects were manageable gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potent Cell-Cycle Inhibition and Upregulation of Immune Response with Abemaciclib and Anastrozole in neoMONARCH, Phase II Neoadjuvant Study in HR+/HER2- Breast Cancer. Hurvitz, SA., Martin, M., Press, MF., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6248378/

Comparative efficacy of different targeted therapies plus ... Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.24.00994

Final Overall Survival in the Phase III FALCON Trial The randomized phase III FALCON trial demonstrated significant improvement in progression-free survival (PFS) with fulvestrant versus anastrozole in ...

3. 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 ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1811714

Overall Survival with Fulvestrant plus Anastrozole in ... The addition of fulvestrant to anastrozole was associated with increased long-term survival as compared with anastrozole alone.

5. 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 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39385327/

Abemaciclib plus non-steroidal aromatase inhibitor or ... Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity ...

7. 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.