Giredestrant vs. Fulvestrant for Advanced Breast Cancer

Recruiting at 415 trial locations

Overseen By Reference Study ID Number: CO44657 https://forpatients.roche.com/

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Hoffmann-La Roche

Must be taking: LHRH agonists

Must not be taking: SERDs, ER-targeting agents

Disqualifiers: Cardiac disease, Liver disease, others

Stay on Your Current Meds

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing two drug combinations to treat a specific type of advanced breast cancer that no longer responds to standard hormone treatments. The goal is to see which combination works better by stopping the cancer cells from growing.

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

The trial information does not specify if you need to stop taking your current medications. However, it does mention that participants should not have had prior systemic therapy for advanced breast cancer.

What data supports the effectiveness of the drug Fulvestrant for advanced breast cancer?

Research shows that Fulvestrant is effective for treating advanced breast cancer in postmenopausal women, especially after other hormone treatments have failed. It has been shown to provide clinical benefits, such as stable disease, in a significant number of patients and is well tolerated with minimal side effects. ^{1 2 3 4 5}

Is Fulvestrant safe for treating advanced breast cancer?

Fulvestrant is generally well tolerated in patients with advanced breast cancer, with only a small percentage experiencing mild adverse events. ^{1 2 4 6 7}

How is the drug Giredestrant different from other treatments for advanced breast cancer?

Giredestrant is a novel drug being compared to Fulvestrant, which is unique because it is an estrogen receptor antagonist that downregulates the estrogen receptor without any agonist effects, making it effective for patients who have become resistant to other endocrine therapies like aromatase inhibitors and selective estrogen receptor modulators. ^{1 3 8 9 10}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with advanced breast cancer that's ER-positive, HER2-negative and has resisted previous endocrine therapy. They must have measurable disease or bone-only disease, be in good physical condition (ECOG PS 0-1), and pre/perimenopausal women and men need to use LHRH agonist therapy. People can't join if they've had certain prior treatments like SERDs, systemic therapies for advanced cancer, have serious heart or liver conditions, or are at immediate risk from their cancer.

Inclusion Criteria

My tumor is estrogen receptor-positive and HER2-negative.

My cancer has a known ESR1 mutation status from a blood test.

My cancer can be measured by scans or is only in my bones.

Exclusion Criteria

I have had treatments like chemotherapy for advanced breast cancer that cannot be surgically removed.

My cancer has spread to vital organs and could cause serious problems soon.

I have previously been treated with drugs targeting estrogen receptors.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive giredestrant or fulvestrant in combination with a CDK4/6 inhibitor

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Abemaciclib (CDK4/6 Inhibitor)
• Fulvestrant (Hormone Therapy)
• Giredestrant (Hormone Therapy)
• LHRH Agonist (Hormone Therapy)
• Palbociclib (CDK4/6 Inhibitor)
• Ribociclib (CDK4/6 Inhibitor)

Trial Overview The study compares the effectiveness of Giredestrant versus Fulvestrant when each is combined with a CDK4/6 inhibitor (chosen by the investigator) in participants who have developed resistance to adjuvant endocrine therapy. It's a Phase III trial where patients are randomly assigned to either treatment group.

Participant Groups

Group I: Giredestrant + Investigator's Choice of CDK4/6i Experimental Treatment 6 Interventions

Participants in the experimental arm will receive giredestrant plus the investigator's choice of CDK4/6 inhibitor (CDK4/6i): palbociclib, ribociclib, or abemaciclib.

Group II: Fulvestrant + Investigator's Choice of CDK4/6i Active Control 6 Interventions

Participants in the control arm will receive fulvestrant plus the investigator's choice of CDK4/6 inhibitor (CDK4/6i): palbociclib, ribociclib, or abemaciclib.

Fulvestrant is already approved in Canada, Japan for the following indications:

Approved in Canada as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in Japan as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Findings from Research

The EFECT trial is the first Phase III study showing that fulvestrant is an effective treatment option for postmenopausal women with advanced breast cancer who have progressed on aromatase inhibitors, demonstrating similar efficacy to exemestane.

Both fulvestrant and exemestane had comparable safety profiles, with no significant differences in adverse events reported, indicating that fulvestrant can be a viable alternative after AI failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant: expanding the endocrine treatment options for patients with hormone receptor-positive advanced breast cancer. Chia, S., Gradishar, W.[2018]

Fulvestrant, an estrogen receptor antagonist, was effective in treating advanced breast cancer in postmenopausal women, showing an overall clinical benefit in 39% of the 339 patients studied, with better outcomes when used as a first-line treatment.

The treatment was well tolerated, with only 5% of patients experiencing adverse events, and it was particularly beneficial for patients with tumors expressing both estrogen and progesterone receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant ("Faslodex"): clinical experience from the Compassionate Use Programme. Steger, GG., Gips, M., Simon, SD., et al.[2018]

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 involving 126 postmenopausal women with advanced breast cancer, fulvestrant demonstrated an objective response rate of 9.5% and a clinical benefit rate of 43.6%, indicating its efficacy as a treatment option after previous endocrine therapies.

Fulvestrant was well tolerated, with only six patients experiencing mild adverse events (grade I/II), suggesting it is a safe option for patients who have progressed on prior treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant ('Faslodex') in pre-treated patients with advanced breast cancer: a single-centre experience. Steger, GG., Bartsch, R., Wenzel, C., et al.[2018]

In a study of 402 postmenopausal women with advanced breast cancer receiving fulvestrant through a Compassionate Use Program, 29.9% experienced clinical benefits, including partial responses and stable disease for over 6 months.

Fulvestrant was well tolerated, with only 1.5% of patients discontinuing treatment due to adverse events, indicating its safety and potential as an effective option for patients who have not responded to previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant (Faslodex) in advanced breast cancer: clinical experience from a Belgian cooperative study. Neven, P., Paridaens, R., Pelgrims, G., et al.[2018]

In a study of 138 premenopausal women with hormone receptor-positive metastatic breast cancer, the combination of fulvestrant and goserelin (F + G) showed a median time to progression of 16.3 months, which was significantly longer than goserelin alone (13.5 months), indicating improved efficacy.

While F + G was associated with some increased joint-related side effects, it demonstrated a favorable safety profile with rare severe toxicities, suggesting it could be a promising treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant plus goserelin versus anastrozole plus goserelin versus goserelin alone for hormone receptor-positive, HER2-negative tamoxifen-pretreated premenopausal women with recurrent or metastatic breast cancer (KCSG BR10-04): a multicentre, open-label, three-arm, randomised phase II trial (FLAG study). Kim, JY., Im, SA., Jung, KH., et al.[2019]

In a study involving 587 postmenopausal women with advanced breast cancer, fulvestrant showed similar efficacy to tamoxifen in patients with hormone receptor-positive tumors, with no significant differences in time to progression (TTP) or objective response rates.

While tamoxifen had a slightly better overall efficacy in the general population, both treatments were well tolerated, indicating that fulvestrant can be a viable option for patients with ER+ and/or PgR+ tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: a multinational, double-blind, randomized trial. Howell, A., Robertson, JF., Abram, P., et al.[2022]

Fulvestrant is a new steroidal estrogen receptor antagonist that effectively downregulates estrogen and progesterone receptors, showing promise as a treatment option for postmenopausal women with advanced breast cancer, especially in cases resistant to tamoxifen and aromatase inhibitors.

Compared to traditional therapies like tamoxifen and selective estrogen receptor modulators, fulvestrant offers a unique mechanism of action with no agonist activity, highlighting its potential role in the sequencing of endocrine therapies for better management of breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endocrine treatment options for advanced breast cancer--the role of fulvestrant. Robertson, JF., Come, SE., Jones, SE., et al.[2018]

Fulvestrant is as effective as anastrozole in treating postmenopausal women with hormone receptor-positive advanced-stage breast cancer, showing similar results in time to progression and other efficacy measures across two phase III trials involving these patients.

Fulvestrant has a favorable safety profile, with low withdrawal rates and fewer adverse events compared to tamoxifen, making it a well-tolerated option for first-line hormonal therapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and tolerability of fulvestrant in postmenopausal women with hormone receptor-positive breast cancer. Jones, SE., Pippen, J.[2019]

Fulvestrant is an effective new endocrine treatment for postmenopausal women with hormone receptor-positive advanced breast cancer, showing similar efficacy to anastrozole and tamoxifen in clinical trials.

Unlike other endocrine therapies, fulvestrant does not exhibit cross-resistance, making it a valuable option for patients who have progressed on prior treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant: a new type of estrogen receptor antagonist for the treatment of advanced breast cancer. Buzdar, AU.[2019]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Fulvestrant: expanding the endocrine treatment options for patients with hormone receptor-positive advanced breast cancer. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Fulvestrant ("Faslodex"): clinical experience from the Compassionate Use Programme. [2018]

3. 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]

4. England pubmed.ncbi.nlm.nih.gov

Fulvestrant ('Faslodex') in pre-treated patients with advanced breast cancer: a single-centre experience. [2018]

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

Fulvestrant (Faslodex) in advanced breast cancer: clinical experience from a Belgian cooperative study. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Fulvestrant plus goserelin versus anastrozole plus goserelin versus goserelin alone for hormone receptor-positive, HER2-negative tamoxifen-pretreated premenopausal women with recurrent or metastatic breast cancer (KCSG BR10-04): a multicentre, open-label, three-arm, randomised phase II trial (FLAG study). [2019]

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

Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: a multinational, double-blind, randomized trial. [2022]

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

Endocrine treatment options for advanced breast cancer--the role of fulvestrant. [2018]

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

Effectiveness and tolerability of fulvestrant in postmenopausal women with hormone receptor-positive breast cancer. [2019]

10. Spain pubmed.ncbi.nlm.nih.gov

Fulvestrant: a new type of estrogen receptor antagonist for the treatment of advanced breast cancer. [2019]