Giredestrant + Palbociclib vs Letrozole + Palbociclib for Breast Cancer

Recruiting at 489 trial locations

Overseen By Reference Study ID Number: BO41843 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: CYP3A inhibitors, CYP3A inducers

Disqualifiers: CNS metastases, Cardiac dysfunction, others

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: 1

Duration: Up to 78 months

992 Participants Needed

Trial Summary

What is the purpose of this trial?

This Phase III, randomized, double-blind, placebo-controlled, multicenter study will evaluate the efficacy and safety of giredestrant combined with palbociclib compared with letrozole combined with palbociclib in patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor-2 (HER2)-negative locally advanced (recurrent or progressed) or metastatic breast cancer.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking strong CYP3A inhibitors or inducers at least 14 days before starting the study treatment. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination of Giredestrant, Letrozole, and Palbociclib for breast cancer?

Research shows that Palbociclib, when combined with Letrozole, significantly improves progression-free survival in postmenopausal women with estrogen receptor-positive, HER2-negative advanced breast cancer. This combination has been shown to enhance the effectiveness of Letrozole, a common breast cancer treatment, by doubling its efficacy while maintaining a manageable safety profile. ^{1 2 3 4 5}

Is the combination of Giredestrant, Letrozole, and Palbociclib safe for treating breast cancer?

Palbociclib, when combined with letrozole, has been shown to be generally safe for treating certain types of breast cancer, with the most common side effect being neutropenia (a low level of white blood cells). This side effect is usually manageable and does not significantly affect patients' quality of life. ^{1 2 3 4 6}

What makes the drug combination of Giredestrant, Letrozole, and Palbociclib unique for breast cancer treatment?

This drug combination is unique because it combines Giredestrant, a novel treatment, with Palbociclib, a first-in-class CDK4/6 inhibitor, and Letrozole, an aromatase inhibitor, to target hormone receptor-positive, HER2-negative advanced breast cancer. Palbociclib enhances the effectiveness of Letrozole by inhibiting specific proteins that help cancer cells grow, offering a potentially more effective treatment option compared to Letrozole alone. ^{1 2 3 7 8}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with ER-positive, HER2-negative advanced or metastatic breast cancer who haven't had systemic anti-cancer therapy for their advanced disease. They should have completed at least 24 months of standard adjuvant endocrine therapy without progression and be over a year since the last treatment. Pre/peri-menopausal women and men must use LHRH agonist therapy.

Inclusion Criteria

I am fully active or can carry out light work.

I am receiving hormone therapy to manage my cancer.

I have cancer that can be measured by scans or have a specific type of bone lesion.

Exclusion Criteria

Pregnant or breastfeeding

Treatment with any investigational therapy within 28 days prior to study treatment

My cancer has spread to vital organs and poses an immediate risk to my life.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive giredestrant combined with palbociclib or letrozole combined with palbociclib

Up to 78 months

Baseline, Days 1 and 15 of Cycles 1 and 2, and Day 1 of each cycle thereafter

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Giredestrant
• Letrozole
• Palbociclib

Trial Overview The study compares the effectiveness and safety of two treatments: Giredestrant combined with Palbociclib versus Letrozole combined with Palbociclib. It's a Phase III trial where participants are randomly assigned to either treatment in a double-blind manner, meaning neither they nor the researchers know which group they're in.

Participant Groups

Group I: Giredestrant + Letrozole-matched Placebo + Palbociclib Experimental Treatment 4 Interventions

Group II: Letrozole + Giredestrant-matched Placebo + Palbociclib Active Control 4 Interventions

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

Palbociclib is the first CDK4/6 inhibitor approved for treating estrogen receptor-positive, HER2-negative metastatic breast cancer, and it works by selectively inhibiting CDK4 and CDK6, enhancing the effects of anti-estrogens like letrozole and fulvestrant.

Clinical trials show that palbociclib significantly doubles the treatment efficacy of letrozole and fulvestrant while maintaining a manageable safety profile, positively impacting patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficacy of palbociclib in the treatment of metastatic breast cancer. Ettl, J., Harbeck, N.[2017]

Oral palbociclib is an effective treatment for HR-positive, HER2-negative advanced or metastatic breast cancer, significantly prolonging progression-free survival when used with letrozole or fulvestrant in clinical trials involving postmenopausal women.

The most common side effect was neutropenia, which was manageable and rarely led to serious complications, indicating that palbociclib can be safely administered without significantly compromising its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib: A Review in HR-Positive, HER2-Negative, Advanced or Metastatic Breast Cancer. Kim, ES., Scott, LJ.[2022]

In a phase 3 study involving 666 postmenopausal women with ER-positive, HER2-negative advanced breast cancer, the combination of palbociclib and letrozole significantly improved progression-free survival to 24.8 months compared to 14.5 months with letrozole alone, indicating its efficacy as a treatment option.

While palbociclib plus letrozole showed better outcomes, it also resulted in higher rates of serious side effects, such as neutropenia (66.4% vs. 1.4% in the placebo group), highlighting the need for careful monitoring of patients during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib and Letrozole in Advanced Breast Cancer. Finn, RS., Martin, M., Rugo, HS., et al.[2022]

Palbociclib, an inhibitor of CDK4 and CDK6, was granted accelerated FDA approval for treating advanced breast cancer in postmenopausal women when combined with letrozole, based on a trial involving 165 patients that showed significant improvement in progression-free survival (PFS).

The trial demonstrated a nearly 50% reduction in the risk of disease progression for patients receiving the combination therapy compared to those on letrozole alone, although the most common side effect noted was neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer. Beaver, JA., Amiri-Kordestani, L., Charlab, R., et al.[2022]

In a study of 666 postmenopausal women with advanced breast cancer, Asian patients receiving palbociclib plus letrozole experienced a significantly longer progression-free survival (PFS) of 25.7 months compared to 13.9 months for those on placebo plus letrozole, indicating the efficacy of this combination treatment.

While hematologic toxicities like neutropenia were more common in Asian patients, they were manageable, and quality of life remained stable, suggesting that palbociclib plus letrozole is a safe and effective treatment option for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib Plus Letrozole as First-Line Therapy in Postmenopausal Asian Women With Metastatic Breast Cancer: Results From the Phase III, Randomized PALOMA-2 Study. Im, SA., Mukai, H., Park, IH., et al.[2023]

In the PALOMA-2 trial involving 666 postmenopausal women with ER+/HER2- advanced breast cancer, the combination of palbociclib and letrozole significantly improved progression-free survival compared to letrozole alone, with a hazard ratio of 0.58.

Neutropenia was the most common adverse event associated with palbociclib, occurring in 95.3% of patients, but it was mostly manageable through dose modifications and did not compromise treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib with Letrozole in Postmenopausal Women with ER+/HER2- Advanced Breast Cancer: Hematologic Safety Analysis of the Randomized PALOMA-2 Trial. Diéras, V., Harbeck, N., Joy, AA., et al.[2020]

In a study with a median follow-up of about 38 months, palbociclib combined with letrozole significantly improved progression-free survival (PFS) in women with advanced estrogen receptor-positive (ER+)/HER2-negative breast cancer, with a median PFS of 27.6 months compared to 14.5 months for the placebo group.

The treatment not only prolonged PFS but also delayed the need for chemotherapy and maintained a favorable safety profile and quality of life for patients, suggesting that palbociclib-letrozole should be the standard first-line therapy for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up. Rugo, HS., Finn, RS., Diéras, V., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

The safety and efficacy of palbociclib in the treatment of metastatic breast cancer. [2017]

2. France pubmed.ncbi.nlm.nih.gov

Palbociclib: A Review in HR-Positive, HER2-Negative, Advanced or Metastatic Breast Cancer. [2022]

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

Palbociclib and Letrozole in Advanced Breast Cancer. [2022]

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

FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer. [2022]

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

Palbociclib Plus Letrozole as First-Line Therapy in Postmenopausal Asian Women With Metastatic Breast Cancer: Results From the Phase III, Randomized PALOMA-2 Study. [2023]

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

Palbociclib with Letrozole in Postmenopausal Women with ER+/HER2- Advanced Breast Cancer: Hematologic Safety Analysis of the Randomized PALOMA-2 Trial. [2020]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up. [2023]

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

Letrozole and palbociclib versus chemotherapy as neoadjuvant therapy of high-risk luminal breast cancer. [2020]