Deescalation of Endocrine Therapy Duration in Women With HR+ HER2- Breast Cancer at Very Low Risk

NCT ID: NCT05297617

Last Updated: 2025-03-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 696 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-12
• Study Completion Date: 2035-11-30

Brief Summary

Hormone therapy is recommended for five years in all patients with hormone receptor-positive breast cancer, but there is no consensus on its duration in low-risk tumours and especially in postmenopausal women. Adjuvant endocrine therapy (ET) is associated with substantial side effects and long-term decreased quality of life.

Moreover, while it has been shown that ET provides a real benefit in reducing the relapse rate over time, the deterioration in quality of life may also have a negative effect on patient adherence to treatment. It is therefore important to offer treatment to women with low-risk cancer less intensive treatment strategies. If recent trials tested longer durations as compared to 5 years for high-risk cancers, older trials have tested shorter durations. The 5-year duration appeared at that time as the gold standard because of optimal benefit-risk ratios of tamoxifen among high-risk patients. However shorter treatments of 2-3 years were already associated with substantial benefits and may be enough for very low risk patients.

Detailed Description

Adjuvant ET is the cornerstone treatment of localized hormone-receptor positive breast cancer, with demonstrated benefits on overall survival (30-40% relative decrease in mortality) but also on the risk of local and contralateral relapse (43-50% relative decrease). While the relative benefit of 5 years ET is identical for small tumors as compared to larger ones, the absolute benefit is much lower, and the risk-benefit ratio may therefore become very questionable given the frequent and impactful side effects of ET. If recent trials tested longer durations as compared to 5 years for high-risk cancers, older trials have tested shorter durations. Five years appeared at that time as the gold standard because of optimal benefit-risk ratios of tamoxifen among rather high-risk patients. However shorter treatments of 2-3 years were already associated with substantial benefits and may be enough for very low risk patients. The purpose of this study is to demonstrate that adjuvant hormone therapy limited to 2 years of antiaromatase in postmenopausal women with a good prognosis can ensure very high survival without metastatic relapse and allows a reduction of side effects and a better quality of life. The 5-year DMFS was excellent in patients with low risk Luminal A tumors who received endocrine therapy.

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Aromatase inhibitor

Patient will receive standard endocrine therapy (single agent aromatase inhibitors) for a maximum of 2 years.

Group Type: EXPERIMENTAL

Anti-aromatase inhibitor

Intervention Type: DRUG

Treatment will be either:

• Letrozole, given per os, 2.5 mg daily
• Anastrozole, given per os, 1 mg daily
• Exemestane, given per os, 25 mg daily

Interventions

Anti-aromatase inhibitor

Treatment will be either:

• Letrozole, given per os, 2.5 mg daily
• Anastrozole, given per os, 1 mg daily
• Exemestane, given per os, 25 mg daily

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Postmenopausal women: Postmenopausal status is defined by any of the following:

• Prior bilateral oophorectomy
• Age ≥60 years
• Age >50 and <60 years and amenorrheic for at least 12 months, and follicle-stimulating hormone (FSH) and estradiol in the postmenopausal range

2. Eastern Cooperative Oncology Group (ECOG) performance status 0-1

3. Women with histologically proven invasive unilateral breast cancer Note: In case of a multifocal invasive tumor, all lesions (maximum 3 infiltrating lesions allowed) must be of identical phenotype and low biological risk

4. M0: Not clinically nor radiologically detectable metastases at time of inclusion

5. Primary tumor completely resected and adequate axillary surgery performed, according to current standards

6. IHC expression of the estrogen receptor and/or progesterone receptor ≥50%

7. HER2 negative according to ASCO criteria in immunohistochemistry and/or genomic analysis (HER2 negativity is defined as IHC 0-1+, or [IHC 2+ and FISH or CISH nonamplified])

8. No indication of adjuvant chemotherapy

9. pT1 (tumor ≤20 mm), pN0, Grade 1 or Grade 2 OR pT2 (tumor ≤30 mm) and pN0, Grade 1 or Grade 2

Note 1: patient with Grade 2 pT2pN0 tumor must be aged under 70 years of age and should receive a genomic test as part of standard care (RIHN reimbursement)

10. Patient considered has having a luminal A ultralow risk of metastatic recurrence (i.e.less than 5% risk of metastatic relapse at 10 years) according to MammaPrint® and Blueprint® tests.

Note 1: To be eligible, MammaPrint index score should be > +0.355

11. Patients eligible to receive or have recently started (with a maximum of 4 months of adjuvant hormone therapy prior to enrollment) an adjuvant hormone therapy (letrozole, anastrozole, or exemestane)

12. Patient is willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures

13. Patients must be affiliated to a Social Security System (or equivalent)

14. Patient must have signed a written informed consent form prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent.

Exclusion Criteria

1. Patients who received a neo-adjuvant hormone therapy, a neo-adjuvant or adjuvant chemotherapy or preoperative medical treatment

2. Any local or regional recurrence or metastatic disease

3. Non-invasive carcinoma

4. Bilateral breast cancer (except in case of contralateral DCIS), or history of other invasive ipsi- or contralateral breast cancer

5. Patients with a history of another malignancy, except for properly treated cervical carcinoma in situ, and non-melanoma cancer of the skin

6. Women with high-risk breast cancer predisposing deleterious germline mutations

7. Contra-indications to the administration of anti-aromatase inhibitors

8. Patients enrolled in another therapeutic study within 30 days prior to inclusion

9. Patients with any other disease or illness, which requires hospitalization or is incompatible with the trial treatment

10. Patients unwilling or unable to comply with trial obligations for geographic, social, physical or psychological reasons, or who are unable to understand the purpose and procedures of the trial

11. Persons deprived of their liberty or under protective custody or guardianship

• Minimum Eligible Age: 51 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Agendia

INDUSTRY

Sponsor Role: collaborator

UNICANCER

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Elise DELUCHE, MD

Role: STUDY_CHAIR

CHU Limoges

Fabrice André, MD

Role: STUDY_CHAIR

Gustave Roussy, Cancer Campus, Grand Paris

Locations

Centre Hospitalier Universitaire de Limoges

Limoges, , France

Site Status: RECRUITING

Institute Gustave Roussy

Villejuif, , France

Site Status: NOT_YET_RECRUITING

Countries

France

Central Contacts

Clara GUYONNEAU, PharmD

Role: CONTACT

c-guyonneau@unicancer.fr

0685167111

Facility Contacts

Elise DELUCHE, MD

Role: primary

Role: backup

elise.deluche@chu-limoges.fr

Fabrice ANDRE, Pr/MD

Role: primary

Role: backup

FABRICE.ANDRE@gustaveroussy.fr

Other Identifiers

2021-002889-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2024-514480-26-00

Identifier Type: CTIS

Identifier Source: secondary_id

UC-BCG-2103

Identifier Type: -

Identifier Source: org_study_id