Giredestrant vs. Fulvestrant for Advanced Breast Cancer

Recruiting at 549 trial locations

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

Age: 18+

Sex: Any

Trial Phase: Phase 3

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 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: Unknown

Duration: Up to 5 years

1050 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, giredestrant and fulvestrant, for advanced breast cancer resistant to some hormone therapies. Researchers aim to determine if these treatments, combined with other drugs targeting cancer cell growth, are safe and effective. The trial targets individuals with a specific type of breast cancer (ER+ and HER2-) who have undergone hormone therapy but not chemotherapy or other advanced treatments. Participants must have a specific gene change (ESR1 mutation) and should not have serious heart or liver problems. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that giredestrant is well-tolerated by patients. Its safety profile resembles that of other hormone treatments, with generally manageable side effects. Common side effects may include hot flashes or fatigue, while serious issues are rare.

Fulvestrant, already used to treat breast cancer, has extensive safety data. It is generally considered safe, with nausea or injection site pain being the most common side effects.

Overall, both giredestrant and fulvestrant have been extensively studied, and their safety is well-established, making them relatively safe options for patients. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for advanced breast cancer?

Researchers are excited about giredestrant for advanced breast cancer because it offers a novel approach by selectively targeting estrogen receptors with high potency, which could lead to more effective tumor suppression. Unlike traditional treatments like fulvestrant, which also targets estrogen receptors but in a different way, giredestrant is a newer type of oral selective estrogen receptor degrader (SERD), potentially offering more convenience and better patient compliance due to its oral administration. Additionally, combining giredestrant with CDK4/6 inhibitors like palbociclib, ribociclib, or abemaciclib could enhance its effectiveness, providing a promising option for those whose cancer progresses despite standard hormone therapies.

What evidence suggests that this trial's treatments could be effective for advanced breast cancer?

In this trial, participants will receive either giredestrant or fulvestrant, each combined with the investigator's choice of a CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib). Previous studies have shown promising results for giredestrant in treating advanced breast cancer that is estrogen receptor-positive (ER+) and HER2-negative. Research indicates that combining giredestrant with everolimus can reduce the risk of the cancer worsening or causing death by 44% in some patients. Giredestrant has also been well tolerated and has shown positive effects against tumors, both alone and with palbociclib, a drug that helps stop cancer cells from growing. These findings suggest that giredestrant could be a strong option for patients with this type of breast cancer who no longer respond to standard hormone treatments. ^{2 3 4 6 7}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Fulvestrant
• Giredestrant
• LHRH Agonist
• Palbociclib
• Ribociclib

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.

How Is the Trial Designed?

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 European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Faslodex for:

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

Approved in United States as Faslodex for:

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

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

Published Research Related to This Trial

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 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]

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 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]

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 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]

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]

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]

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 (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]

Citations

1. roche.com roche.com/media/releases/med-cor-2025-10-18

Roche's phase III evERA data showed giredestrant ... Giredestrant plus everolimus reduced the risk of disease progression or death by 44% and 62% in ITT and ESR1-mutated populations, ...

2. dana-farber.org dana-farber.org/newsroom/news-releases/2025/novel-treatment-combination-improves-progression-free-survival-in-metastatic-estrogen-receptor-positive-her-2-negative-breast-cancer

Novel Treatment Combination Improves Progression-Free ... Patients with estrogen-receptor positive HER2 negative advanced breast cancer showed significantly improved progression-free survival when ...

3. onclive.com onclive.com/view/giredestrant-everolimus-extends-pfs-for-er-her2--advanced-breast-cancer

Giredestrant/Everolimus Extends PFS for ER+, HER2 Giredestrant plus everolimus improved progression-free survival in ER-positive, HER2-negative advanced breast cancer after a prior CDK4/6 ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.01500

Giredestrant for Estrogen Receptor–Positive, HER2- ... Giredestrant is well tolerated, and has shown encouraging antitumor activity in aBC as a monotherapy and in combination with palbociclib, ...

5. cancernetwork.com cancernetwork.com/view/giredestrant-combo-significantly-boosts-pfs-in-er-advanced-breast-cancer

Giredestrant Combo Significantly Boosts PFS in ER+ ... Data from the phase 3 evERA trial show a trend toward improved overall survival with giredestrant plus everolimus in this breast cancer ...

6. roche.com roche.com/media/releases/med-cor-2025-09-22

Positive phase III results show Roche's giredestrant ... Positive phase III results show Roche's giredestrant significantly improved progression-free survival in ER-positive advanced breast cancer.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38537155/

Giredestrant for Estrogen Receptor-Positive, HER2- ... Giredestrant was well tolerated, with a safety profile comparable to PCET and consistent with known endocrine therapy risks.