Fulvestrant + Anastrozole for Breast Cancer

Recruiting at 866 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Alliance for Clinical Trials in Oncology

Must be taking: Anastrozole, Fulvestrant

Must not be taking: Hormone replacement

Disqualifiers: Premenopausal, Inflammatory breast cancer, 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)

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

Compensation: Varies

Number of Visits: 1

1473 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but it does mention that hormone replacement therapy, megestrol acetate, or raloxifene should not be taken within one week before joining the study.

What data supports the effectiveness of the drug combination of Fulvestrant and Anastrozole for breast cancer?

Research shows that the combination of Fulvestrant and Anastrozole is more effective than Anastrozole alone for treating hormone receptor-positive advanced breast cancer, providing a valuable option for patients. ^{1 2 3 4 5}

Is the combination of Fulvestrant and Anastrozole safe for humans?

Anastrozole (Arimidex) has been shown to have a lower incidence of gynecologic side effects compared to tamoxifen in breast cancer treatment, indicating a favorable safety profile. However, specific safety data for the combination of Fulvestrant and Anastrozole is not provided in the available research. ^{3 4 6 7 8}

How is the drug combination of Fulvestrant and Anastrozole unique for treating breast cancer?

The combination of Fulvestrant and Anastrozole is unique because it combines two different mechanisms: Fulvestrant degrades estrogen receptors, while Anastrozole reduces estrogen production. This combination has been shown to be more effective than Anastrozole alone in treating hormone receptor-positive metastatic breast cancer. ^{1 2 5 9 10}

What is the purpose of this trial?

The study is being conducted to determine whether neoadjuvant endocrine therapy with fulvestrant or the combination of anastrozole and fulvestrant, is better than anastrozole when given before surgery to shrink the cancer and stop it from growing. Anastrozole inhibits tumor growth by reducing the levels of estrogen and has been approved by the Food and Drug Administration (FDA) of the United States for use after surgery for postmenopausal women with estrogen receptor positive breast cancer. It is also considered a standard of care to give anastrozole for a few months before surgery to shrink the tumor. Fulvestrant inhibits tumor cell growth by reducing the levels of estrogen receptor in the tumor cell. It is not approved by the FDA for use in women with early stage breast cancer before or after surgery, but is approved by the FDA for patients with advanced (Stage 4) estrogen receptor positive breast cancer that has spread to other parts of the body.

Research Team

Cynthia Ma, MD, PhD

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

Postmenopausal women with Stage II-III estrogen receptor positive breast cancer, who have not started any treatment and are planning to undergo surgery. Participants must be at least 18 years old, have a specific score indicating the presence of estrogen receptors in their tumor cells, and meet certain health criteria based on blood tests and physical exams.

Inclusion Criteria

I am able to care for myself and perform daily activities.

My breast cancer is estrogen receptor positive with a high Allred score or high ER positivity.

Your recent lab test results need to meet certain standards.

Exclusion Criteria

I have not gone through menopause.

My breast cancer involves redness of the breast or skin invasion.

I have had a surgical biopsy for my breast cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Endocrine Treatment

Participants receive neoadjuvant endocrine therapy with either anastrozole, fulvestrant, or a combination of both for 24 weeks to shrink the tumor before surgery

24 weeks

Multiple visits for drug administration and monitoring

Surgery

Participants undergo surgery to remove the tumor after completing neoadjuvant endocrine therapy

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after surgery and treatment

5 years

Treatment Details

Interventions

• Anastrozole
• Fulvestrant

Trial Overview The trial is testing whether taking fulvestrant alone or combined with anastrozole before surgery is more effective than just anastrozole for shrinking tumors. Anastrozole lowers estrogen to inhibit tumor growth and is standard care pre-surgery; fulvestrant decreases estrogen receptors in tumor cells but isn't approved for early-stage use yet.

Participant Groups

Group I: Arm III (anastrozole and fulvestrant) Active Control 2 Interventions

Patients receive anastrozole daily in combination with fulvestrant on days 1 and 15 of cycle 1, and on day 1 of cycles 2-6 followed by surgery. A treatment cycle is 4 weeks in length. After completion of analysis of endocrine resistant data, patients will continue treatment as defined in the protocol.

Group II: Arm I (anastrozole) Active Control 1 Intervention

Patients receive anastrozole daily for 6 cycles followed by surgery. A treatment cycle is 4 weeks in length. After completion of analysis of endocrine resistant data, patients will continue treatment as defined in the protocol.

Group III: Arm II (fulvestrant) Active Control 1 Intervention

Patients receive fulvestrant on days 1 and 15 of cycle 1 and day 1 of cycles 2-6 followed by surgery. A treatment cycle is 4 weeks in length. After completion of analysis of endocrine resistant data, patients will continue treatment as defined in the protocol.

Anastrozole is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Arimidex for:

• Breast cancer
• Early breast cancer in postmenopausal women

Approved in United States as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• First-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer

Approved in Canada as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• Treatment of postmenopausal women with hormone receptor-positive advanced breast cancer

Approved in Japan as Arimidex for:

• Breast cancer

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Fulvestrant (Faslodex) is as effective as anastrozole (Arimidex) for treating advanced breast cancer in postmenopausal women, with similar objective response rates across different patient subgroups.

Both treatments provided comparable clinical benefits, making fulvestrant a valuable option for patients with visceral metastases who have not responded to previous endocrine therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant (Faslodex) versus anastrozole for the second-line treatment of advanced breast cancer in subgroups of postmenopausal women with visceral and non-visceral metastases: combined results from two multicentre trials. Mauriac, L., Pippen, JE., Quaresma Albano, J., et al.[2019]

In a study of 6241 postmenopausal women with early-stage breast cancer, anastrozole was found to have significantly fewer treatment-related adverse events compared to tamoxifen, indicating better tolerability.

Anastrozole also demonstrated a more favorable risk-benefit profile, with lower rates of serious adverse events and recurrence compared to tamoxifen, making it a preferable option for adjuvant treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial. Buzdar, A., Howell, A., Cuzick, J., et al.[2022]

Anastrozole is as effective as tamoxifen for treating advanced breast cancer in postmenopausal women, showing a slightly higher objective response rate (21% vs. 17%) and a significant clinical benefit in 59% of patients compared to 46% for tamoxifen.

Anastrozole offers a significant advantage in time to progression (median of 11.1 months vs. 5.6 months for tamoxifen) and has a lower incidence of side effects, such as thromboembolic events and vaginal bleeding, making it a preferable first-line therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. Arimidex Study Group. Nabholtz, JM., Buzdar, A., Pollak, M., et al.[2022]

In a retrospective analysis of the ATAC trial, women taking tamoxifen experienced significantly more gynecologic adverse events (34.2%) compared to those taking anastrozole (20.5%), leading to more medical interventions, including a nearly fourfold increase in hysterectomies.

The findings support the use of anastrozole as the preferred initial treatment for early hormone receptor-positive breast cancer due to its lower incidence of gynecologic complications, particularly since most adverse events with tamoxifen occurred within the first 2.5 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A lower incidence of gynecologic adverse events and interventions with anastrozole than with tamoxifen in the ATAC trial. Duffy, SR., Distler, W., Howell, A., et al.[2018]

Anastrozole is a potent and selective third-line aromatase inhibitor that offers a significant advancement in the treatment of hormone-sensitive breast cancer, particularly for postmenopausal women.

This review highlights anastrozole's biochemical properties and clinical efficacy, indicating its widespread use as a first- and second-line treatment option, potentially providing better outcomes and safety compared to traditional therapies like tamoxifen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anastrozole: pharmacological and clinical profile in postmenopausal women with breast cancer. Köberle, D., Thürlimann, B.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Fulvestrant (Faslodex) versus anastrozole for the second-line treatment of advanced breast cancer in subgroups of postmenopausal women with visceral and non-visceral metastases: combined results from two multicentre trials. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Fulvestrant decreases anastrozole drug concentrations when taken concurrently by patients with metastatic breast cancer treated on SWOG study S0226. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial. [2022]

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

Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. Arimidex Study Group. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Anastrozole plus fulvestrant vs. anastrozole alone for hormone receptor-positive advanced breast cancer: a meta-analysis of randomized controlled trials. [2020]

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

Influence of comorbidities and age on risk of death without recurrence: a retrospective analysis of the Arimidex, Tamoxifen Alone or in Combination trial. [2022]

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

A lower incidence of gynecologic adverse events and interventions with anastrozole than with tamoxifen in the ATAC trial. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Anastrozole: pharmacological and clinical profile in postmenopausal women with breast cancer. [2018]

9. Thailand pubmed.ncbi.nlm.nih.gov

Fulvestrant 250 mg versus anastrozole 1 mg in the treatment of advanced breast cancer: a meta-analysis of randomized controlled trials. [2019]

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

Fulvestrant: A Review in Advanced Breast Cancer Not Previously Treated with Endocrine Therapy. [2018]