What is the mechanism of action of this treatment?

Selective Estrogen Receptor Degraders (SERDs) like Giredestrant work by binding to estrogen receptors on breast cancer cells, leading to receptor degradation and downregulation, which inhibits the cancer cells' growth. This is crucial for patients with estrogen receptor-positive breast cancer, as it directly targets the hormone-driven growth mechanism. In comparison, Selective Estrogen Receptor Modulators (SERMs) such as tamoxifen block estrogen receptors, and aromatase inhibitors like anastrozole reduce estrogen production. Understanding these mechanisms helps patients and doctors choose the most effective treatment based on the cancer's specific characteristics and resistance patterns.

What side effects are associated with this type of intervention?

Common treatments for estrogen receptor-positive breast cancer include Selective Estrogen Receptor Degraders (SERDs) like Giredestrant, Selective Estrogen Receptor Modulators (SERMs) like tamoxifen, and aromatase inhibitors such as anastrozole. Known side effects of SERDs can include hot flashes, fatigue, and gastrointestinal disturbances. SERMs like tamoxifen may cause vasomotor symptoms, vaginal discharge, nausea, depression, and an increased risk of thromboembolic events and endometrial carcinoma. Aromatase inhibitors are associated with bone density loss, fractures, and cardiovascular risks.

What prior FDA approvals exist?

The FDA has approved several treatments for breast cancer that target estrogen receptors, similar to giredestrant. Notable examples include tamoxifen, a selective estrogen receptor modulator (SERM), and fulvestrant, another SERD. Tamoxifen has been widely used for decades to treat estrogen receptor-positive breast cancer by blocking estrogen receptors. Fulvestrant, on the other hand, works by degrading estrogen receptors and is used in postmenopausal women with hormone receptor-positive metastatic breast cancer. These therapies are part of the broader category of endocrine treatments aimed at inhibiting the growth-promoting effects of estrogen on breast cancer cells.

What other types of research exist?

Promising novel alternatives to Giredestrant for breast cancer patients include Elacestrant, another selective estrogen receptor degrader (SERD) that has shown efficacy in clinical trials. Additionally, novel therapies such as oral SERDs like Rintodestrant and targeted therapies like Alpelisib (a PI3K inhibitor) for patients with PIK3CA mutations are also considered promising options.

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Giredestrant + Hormone Therapy for Early-Stage Breast Cancer

Phase 3

Recruiting

Research Sponsored by Hoffmann-La Roche

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Documented estrogen receptor (ER)-positive and HER2-negative breast tumor, as assessed locally on a primary disease specimen

Participants must have undergone definitive surgery of their primary breast tumor(s) and axillary lymph nodes (axillary lymph node dissection [ALND] and/or sentinel lymph node biopsy [SLNB])

Must not have

Active cardiac disease or history of cardiac dysfunction

Diagnosed with Stage IV breast cancer

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from randomization to death from any cause (up to 10 years)

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing giredestrant, a medication given after initial treatment to prevent breast cancer from returning. It focuses on patients with a specific type of early-stage breast cancer that is hormone-driven and at higher risk of recurrence. Giredestrant works by blocking the hormone estrogen from helping cancer cells grow. Giredestrant has shown promise in previous studies.

Who is the study for?

This trial is for adults with early-stage, estrogen receptor-positive, HER2-negative breast cancer who've had surgery and possibly chemotherapy (with a 21-day gap before joining the study). They should be within 12 months post-surgery, have no prior endocrine therapy or other cancers in the last 3 years, and must not be pregnant. Good organ function and performance status are required.

What is being tested?

The study compares Giredestrant, a new drug for breast cancer treatment after surgery (adjuvant), to standard endocrine therapies chosen by physicians. It's an open-label Phase III trial where participants are randomly assigned to either treatment group.

What are the potential side effects?

Potential side effects of Giredestrant may include symptoms like nausea, fatigue, hot flashes, joint pain or changes in liver function tests. The exact side effects will vary depending on individual responses and the specific endocrine therapy used as a comparison.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My breast cancer is estrogen receptor positive and HER2 negative.

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I have had surgery to remove my breast tumor and lymph nodes.

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

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My breast cancer is estrogen receptor positive and HER2 negative.

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I have had surgery to remove my breast tumor and lymph nodes.

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I finished my additional chemotherapy at least 21 days ago.

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I can take care of myself and am up and about more than half of my waking hours.

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I can take pills without any issues.

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My breast cancer is estrogen receptor positive and HER2 negative.

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I have had surgery to remove my breast tumor and lymph nodes.

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I finished my additional chemotherapy at least 3 weeks ago.

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I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have heart problems or have had them in the past.

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My breast cancer is at stage IV.

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I have severe liver disease, such as hepatitis or cirrhosis.

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I haven't taken strong CYP3A4 affecting drugs recently.

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I am pre- or perimenopausal, or a male with a known allergy to LHRH agonists.

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I have a history of bleeding disorders or blood clots.

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I need dialysis for my kidney condition.

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I have not had major surgery unrelated to breast cancer in the last 28 days.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from randomization to death from any cause (up to 10 years)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from randomization to death from any cause (up to 10 years)

This trial's timeline: 3 weeks for screening, Varies for treatment, and from randomization to death from any cause (up to 10 years) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Invasive Disease-Free Survival (IDFS), Excluding Second Primary Non-Breast Cancers

Secondary study objectives

Change from Baseline in the EQ 5D-5L Index-Based Score at Specified Timepoints

Change from Baseline in the EQ 5D-5L Visual Analogue Scale (VAS) Score at Specified Timepoints

Change from Baseline in the Mean Global Health Status/Quality of Life (QoL) Scale Score at Specified Timepoints, Assessed Using the EORTC QLQ-C30

+12 more

Side effects data

From 2021 Phase 2 trial • 221 Patients • NCT04436744

41%

Neutropenia

23%

Neutrophil count decreased

22%

Asthenia

14%

Nausea

14%

Hot flush

13%

Leukopenia

13%

White blood cell count decreased

11%

Anaemia

11%

Arthralgia

Fatigue

Mucosal inflammation

Diarrhoea

Vomiting

Rash

Alopecia

Headache

Constipation

Procedural pain

Hip fracture

COVID-19

Pyrexia

Myocardial infarction

Uterine perforation

Aspartate aminotransferase increased

Alanine aminotransferase increased

100%

80%

60%

40%

20%

Study treatment Arm

Giredestrant + Palbociclib

Anastrozole + Palbociclib

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Arm A: GiredestrantExperimental Treatment2 Interventions

Group II: Arm B: Endocrine Therapy of Physician's ChoiceActive Control2 Interventions

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Giredestrant

2019

Completed Phase 2

~300

LHRH Agonist

2013

Completed Phase 2

~130

0 / 20Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Selective Estrogen Receptor Degraders (SERDs) like Giredestrant work by binding to estrogen receptors on breast cancer cells, leading to receptor degradation and downregulation, which inhibits the cancer cells' growth. This is crucial for patients with estrogen receptor-positive breast cancer, as it directly targets the hormone-driven growth mechanism. In comparison, Selective Estrogen Receptor Modulators (SERMs) such as tamoxifen block estrogen receptors, and aromatase inhibitors like anastrozole reduce estrogen production. Understanding these mechanisms helps patients and doctors choose the most effective treatment based on the cancer's specific characteristics and resistance patterns.

Premenopausal women with early breast cancer treated with estradiol suppression have severely deteriorated bone microstructure.Molecular mechanisms of endocrine resistance and their implication in the therapy of breast cancer.