Giredestrant vs. Fulvestrant for Advanced Breast Cancer
Recruiting in Palo Alto (17 mi)
+415 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Hoffmann-La Roche
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.
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.
13459Is 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.
267910What 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.
16789Do 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.
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.
I haven't had any drug treatments for my advanced cancer.
I am taking hormone therapy as required if I am a pre/perimenopausal woman or a man.
My breast cancer cannot be cured with surgery or radiation.
I can carry out all my daily activities without help.
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.
I have heart problems or a history of heart issues.
I have a significant history of liver problems.
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: Giredestrant + Investigator's Choice of CDK4/6iExperimental Treatment6 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 CDK4/6iActive Control6 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
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Cancer Specialists of North FloridaJacksonville, FL
Rocky Mountain Cancer CentersDenver, CO
Texas Oncology Cancer CenterAustin, TX
Winship Cancer Institute of Emory UniversityAtlanta, GA
More Trial Locations
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Who is running the clinical trial?
Hoffmann-La RocheLead Sponsor
References
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]The efficacy of fulvestrant (Faslodex), a novel oestrogen receptor (ER) antagonist that downregulates the ER and has no known agonist effects, was compared with the aromatase inhibitor anastrozole (Arimidex) for the second-line treatment of advanced breast cancer in postmenopausal women with visceral and non-visceral metastases. Assessment was by means of a retrospective subgroup analysis of combined data from two randomised, phase III trials. Objective response (OR) rates were similar in patients treated with fulvestrant and anastrozole, respectively (21.9% versus 19.3%-patients with no visceral metastases; 15.7% versus 13.2%-all of the patients with visceral metastases; 18.8% versus 14.0%-patients with visceral metastases only). The proportion of patients with clinical benefit (CB) was also similar between treatments and between subgroups with and without visceral disease. Fulvestrant is at least as effective as anastrozole, providing a valuable treatment option for advanced breast cancer in postmenopausal women with visceral metastases who have failed on prior endocrine therapy.
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]To evaluate the efficacy and tolerability of fulvestrant (Faslodex; AstraZeneca Pharmaceuticals LP, Wilmington, DE), a new estrogen receptor (ER) antagonist that downregulates ER and has no agonist effects, versus tamoxifen, an antiestrogen with agonist and antagonist effects, for the treatment of advanced breast cancer in postmenopausal women.
Fulvestrant: a new type of estrogen receptor antagonist for the treatment of advanced breast cancer. [2019]Postmenopausal women with hormone receptor- positive tumors are candidates for endocrine treatment. Current treatment options include the selective estrogen receptor modulators (e.g., tamoxifen and toremifene), which inhibit estrogen receptor signaling, and the aromatase inhibitors (e.g., anastrozole and letrozole), which prevent the conversion of androgens into estrogen in postmenopausal women. As most patients eventually become resistant to endocrine agents, there is a need for new treatments that are effective, well tolerated and lack cross-resistance with currently available therapies. This review describes the development of fulvestrant (Faslodex), a new type of endocrine agent, which is an estrogen receptor antagonist with no agonist effects. Phase III clinical trials have found that fulvestrant is as effective and well tolerated as anastrozole for treating postmenopausal patients with advanced breast cancer who have progressed on one prior endocrine therapy. In addition, fulvestrant has first-line efficacy similar to that of tamoxifen in patients with estrogen receptor-positive and/or progesterone receptor-positive breast cancer. Moreover, in a compassionate-use program, it has become clear that fulvestrant is not cross-resistant with other therapies. Therefore, fulvestrant is a versatile new treatment option for postmenopausal women with advanced breast cancer who have progressed on prior endocrine therapy.
Endocrine treatment options for advanced breast cancer--the role of fulvestrant. [2018]For many years, tamoxifen has been the 'gold standard' amongst anti-oestrogen therapies for breast cancer. However, the selective aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, have demonstrated advantages over tamoxifen as first-line treatments for advanced disease. Anastrozole is also more effective as an adjuvant treatment in early, operable breast cancer and is being increasingly used in the adjuvant setting. Generally, the selective oestrogen receptor modulators (SERMs), such as toremifene, droloxifene, idoxifene, raloxifene, and arzoxifene, show minimal activity in tamoxifen-resistant disease and show no superiority over tamoxifen as first-line treatments. In addition to these agents, other treatment options for advanced disease include high-dose oestrogens and progestins. Response rates for high-dose oestrogens and tamoxifen are similar, but the use of oestrogens is limited by their toxicity profile. Consequently, there is a need for new endocrine treatment options for breast cancer, particularly for use in disease that is resistant to tamoxifen or AIs. Fulvestrant ('Faslodex') is a new type of steroidal oestrogen receptor (ER) antagonist that downregulates cellular levels of the ER and progesterone receptor and has no agonist activity. This paper reviews the key efficacy and tolerability data for fulvestrant in postmenopausal women in the context of other endocrine therapies and explores the potential role of fulvestrant within the sequencing of endocrine therapies for advanced breast cancer.
Effectiveness and tolerability of fulvestrant in postmenopausal women with hormone receptor-positive breast cancer. [2019]Fulvestrant, an estrogen receptor antagonist that downregulates the estrogen receptor but has no known agonist effects, has been evaluated in 2 randomized trials involving postmenopausal women with hormone receptor-positive, progressive advanced-stage breast cancer after disease progression with antiestrogen therapy. These phase III studies, from which data were reported separately and in a planned combined analysis, showed that fulvestrant 250 mg per month intramuscularly was at least as effective as anastrozole 1 mg per day orally with respect to the primary endpoint of time to progression as well as secondary efficacy endpoints, which included objective response, clinical benefit, and survival. Both trials showed that patients treated with fulvestrant had a significantly longer duration of response, and a retrospective analysis found that pretreatment with fulvestrant did not preclude response to third-line hormonal therapy. More recently, fulvestrant was shown to be active as first-line hormonal therapy for advanced-stage breast cancer, with overall efficacy similar to that of tamoxifen in patients with hormone receptor-positive disease. Fulvestrant has been well tolerated in comparative trials published to date, translating into low study withdrawal rates and maintenance of quality of life. The incidence of adverse events was similar between the treatment arms in both trials of fulvestrant versus anastrozole, but it was notably lower for fulvestrant relative to tamoxifen in the first-line setting. In light of the results of comparative phase III trials, fulvestrant is effective and well tolerated in the treatment of postmenopausal women with hormone receptor-positive advanced-stage breast cancer.
Fulvestrant ("Faslodex"): clinical experience from the Compassionate Use Programme. [2018]Fulvestrant ("Faslodex") is a new oestrogen receptor (ER) antagonist with no agonist effects that is licensed in the USA, Brazil, Europe and elsewhere for the treatment of advanced breast cancer (ABC) in postmenopausal women following progression on other endocrine agents. This report consolidates clinical experience from the "Faslodex" Compassionate Use Programme, including a total of 339 patients treated at eight cancer centres. Patients received fulvestrant as first- (n=22), second- (n=125), third- (n=105), fourth- (n=58), fifth- (n=22) or sixth-line (n=5) hormonal treatment for ABC, with two patients receiving fulvestrant after more than six other endocrine therapies. Objective response was achieved by 40 patients and stable disease lasting 6 months by 92 patients, giving overall clinical benefit (CB) in 132/339 patients (39%). The CB rate decreased as fulvestrant was used later in the sequence of endocrine treatments, from 46% (10/22) with first-line fulvestrant to 27% (6/22) with fifth-line fulvestrant. Increased benefit was found in patients with tumours expressing both ER and progesterone receptor (PgR) compared with other combinations, although good activity was reported in patients expressing either ER or PgR as well as in tumours expressing human epidermal growth factor receptor 2. Fulvestrant was well tolerated; adverse events were noted in 18/339 patients (5%). These findings concur with data from the clinical-trial setting and further support the assertion that greater benefit is derived when fulvestrant is used early in the treatment sequence.
Fulvestrant ('Faslodex') in pre-treated patients with advanced breast cancer: a single-centre experience. [2018]Fulvestrant ('Faslodex') is a new oestrogen receptor (ER) antagonist with no agonist effects. This report describes the experience of a single centre including 126 postmenopausal women with advanced breast cancer (ABC) in a fulvestrant Compassionate Use Programme. All patients had previously received endocrine treatment for early or ABC. Patients received fulvestrant as first- (n=7), second- (n=51), third- (n=50) or fourth-line endocrine therapy (n=18) for ABC (median duration of treatment: 4 months [range 3-27(+) months], follow-up: 13 months [range 1-38(+) months]). Twelve patients had partial responses (PR) and 43 patients experienced stable disease (SD) > or = 6 months (objective response rate: 9.5%; clinical benefit [CB] rate: 43.6%). Ten of 12 patients with a PR had HER2-negative tumours, and 9/12 had ER-positive and progesterone receptor (PgR)-positive disease (two patients had unknown HER2 status and one had unknown ER and PgR status). Nine of the 18 patients with HER2-positive tumours experienced CB with fulvestrant. Although CB rates were similar when fulvestrant was given as first- to fourth-line endocrine treatment, the proportion of those experiencing CB who had a PR appeared to decrease when fulvestrant was used later in the sequence. Fulvestrant was well tolerated; six patients experienced adverse events (all grade I/II). These data demonstrate that fulvestrant is an effective and well-tolerated therapy for patients with ABC progressing on prior therapies.
Fulvestrant (Faslodex) in advanced breast cancer: clinical experience from a Belgian cooperative study. [2018]Fulvestrant (Faslodex) is a new estrogen receptor (ER) antagonist with no agonist effects that is licensed for the treatment of postmenopausal women with hormone-sensitive advanced breast cancer (ABC) who have progressed/recurred on prior antiestrogen therapy. The Faslodex Compassionate Use Program (CUP) provides expanded access to fulvestrant in countries where it is not yet available for patients who are not eligible to enter clinical trials. This analysis pools data from 402 patients who received fulvestrant as part of the CUP in Belgium, predominantly as 3rd- to 5th-line endocrine therapy for ABC. Two patients experienced partial responses and 118 experienced stable disease lasting>or=6 months, resulting in an overall clinical benefit rate of 29.9%. Fulvestrant was active in patients with multiple sites of metastases, visceral metastases, human epidermal growth factor receptor 2-positive disease and after heavy endocrine pre-treatment. Fulvestrant was well tolerated, with only six patients (1.5%) discontinuing treatment following adverse events. These data support the findings of previous CUP analyses and Phase II and III trials, suggesting that fulvestrant is a valuable addition to the treatment sequence for postmenopausal women with ABC who have progressed/recurred on prior endocrine therapy.
Fulvestrant: expanding the endocrine treatment options for patients with hormone receptor-positive advanced breast cancer. [2018]With the aromatase inhibitors (AIs) replacing tamoxifen as the first-line treatment for postmenopausal women with hormone receptor-positive early and advanced breast cancer, there is a need to evaluate appropriate endocrine treatment options following AI failure. However, until recently, there were no Phase III trial data in this area. Fulvestrant (Faslodex) is an oestrogen receptor antagonist utilised for the treatment of postmenopausal women with locally advanced or metastatic breast cancer following progression or recurrence on anti-oestrogen therapy. Fulvestrant has a mode of action that is distinct from the AIs and the selective oestrogen receptor modulators, and thus may offer an effective treatment option in the post-AI setting. The Evaluation of Faslodex and Exemestane Clinical Trial (EFECT) is the first Phase III trial to evaluate the efficacy and tolerability of fulvestrant and the steroidal AI, exemestane, in patients with locally advanced or metastatic breast cancer who have progressed or recurred while receiving a non-steroidal AI. EFECT confirmed that fulvestrant and exemestane offer effective treatment options in this setting. Similar efficacy was seen in both treatment groups and there were no significant differences in reported adverse events between fulvestrant and exemestane. The EFECT data provide further evidence for the activity of fulvestrant in the treatment of advanced breast cancer. Other ongoing fulvestrant trials will further define its full role, including the potential for a high-dose regimen, combination of fulvestrant with an AI, and identification of clinical and biological markers to help in targeting those patients who are most likely to respond to treatment.
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]We investigated the efficacy and safety of fulvestrant plus goserelin (F + G) versus anastrozole plus goserelin (A + G) in comparison with goserelin (G) alone in premenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), tamoxifen-pretreated metastatic breast cancer (MBC).