What side effects are associated with this type of intervention?

Common treatments for breast cancer, particularly those similar to Giredestrant (a Selective Estrogen Receptor Degrader - SERD), include SERDs, CDK4/6 inhibitors, and other endocrine therapies. SERDs like Giredestrant and Fulvestrant can cause hot flashes, fatigue, nausea, and injection site reactions. CDK4/6 inhibitors such as palbociclib, ribociclib, and abemaciclib often lead to neutropenia, leukopenia, fatigue, nausea, diarrhea, and alopecia. Endocrine therapies like tamoxifen and aromatase inhibitors are associated with hot flashes, joint pain, bone density loss, and an increased risk of thromboembolic events.

What prior FDA approvals exist?

The FDA has approved several treatments for breast cancer, particularly focusing on hormonal therapies for estrogen receptor-positive (ER+) types. Fulvestrant, another SERD, is commonly used and has shown efficacy in combination with CDK4/6 inhibitors like palbociclib, ribociclib, and abemaciclib. Other hormonal agents such as tamoxifen, a selective estrogen receptor modulator (SERM), and aromatase inhibitors like anastrozole and letrozole, have also been approved and are widely used in the treatment of ER+ breast cancer. These treatments aim to block or degrade estrogen receptors, thereby inhibiting the growth of hormone-dependent cancer cells.

What other types of research exist?

Promising novel alternatives to Giredestrant for breast cancer patients in 2024 include: 1) Elacestrant, another SERD that has shown positive results in clinical trials for ER+ breast cancer. 2) CDK4/6 inhibitors like Abemaciclib, Ribociclib, and Palbociclib, which are often used in combination with endocrine therapies. 3) Oral selective estrogen receptor modulators (SERMs) such as Lasofoxifene, which is being investigated for its efficacy in ER+ breast cancer. 4) Novel targeted therapies like Alpelisib, a PI3K inhibitor, for patients with PIK3CA-mutated breast cancer.

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Hormone Therapy

Giredestrant vs. Fulvestrant for Advanced 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-positive (ER+), HER2-negative (HER2-) tumor assessed locally on the most recent tumor biopsy (or archived tumor sample)

Confirmed ESR1 mutation status (ESR1m vs. ESR1nmd) in baseline circulating tumor DNA (ctDNA) through central laboratory testing

Must not have

Prior systemic therapy (e.g., prior chemotherapy, immunotherapy, or biologic therapy) for locally advanced unresectable or metastatic breast cancer

Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from randomization until end of follow-up (up to 5 years)

Awards & highlights

Pivotal Trial

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include hot flashes, nausea, injection site reactions from Fulvestrant; fatigue, diarrhea from CDK4/6 inhibitors; and potential unknown side effects from Giredestrant as it's newer.

Eligibility Criteria

Inclusion Criteria

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

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

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

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

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I haven't had any drug treatments for my advanced cancer.

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I am taking hormone therapy as required if I am a pre/perimenopausal woman or a man.

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My breast cancer cannot be cured with surgery or radiation.

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I can carry out all my daily activities without help.

Exclusion Criteria

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

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

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

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I have previously been treated with drugs targeting estrogen receptors.

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I have heart problems or a history of heart issues.

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I have a significant history of liver problems.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from randomization until end of follow-up (up to 5 years)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from randomization until end of follow-up (up to 5 years)

This trial's timeline: 3 weeks for screening, Varies for treatment, and from randomization until end of follow-up (up to 5 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

Progression-Free Survival (PFS) in the ESR1 mutation (ESR1m) Subgroup

Secondary study objectives

Clinical Benefit Rate (CBR)

Confirmed Objective Response Rate (cORR)

Duration of Response (DOR)

+9 more

Awards & Highlights

Pivotal Trial

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

No Placebo-Only Group

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

Trial Design

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ribociclib

2018

Completed Phase 3

~2420

Abemaciclib

2019

Completed Phase 2

~1890

Giredestrant

2019

Completed Phase 2

~300

Palbociclib

2017

Completed Phase 3

~3790

LHRH Agonist

2013

Completed Phase 2

~130

0 / 12Eligibility 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 driven by estrogen. This is crucial for patients with estrogen receptor-positive (ER+), HER2-negative breast cancer, as their tumors rely on estrogen signaling for proliferation. Other common treatments include aromatase inhibitors, which reduce estrogen production, and CDK4/6 inhibitors, which block proteins that promote cell division. These therapies are essential as they target the specific pathways that fuel cancer growth, offering more effective and personalized treatment options for patients.

A review of an unfavorable subset of breast cancer: estrogen receptor positive progesterone receptor negative.