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

Официальное название

Single-arm Study to De-escalate Adjuvant Endocrine Therapy Duration in Women With HR+ HER2- Breast Cancer at Very Low Risk of Metastasis

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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

Первичные конечные точки

• Distant relapse-free interval (DRFI) [Срок оценки: From date of beginning of hormonotherapy to onset of metastases or death, up to 5-years.]

Вторичные конечные точки (12)

• Distant Disease-Free Survival (DDFS) [Срок оценки: From date of beginning of hormonotherapy to the date of first event of distant recurrence, death from any cause or secondary non-breast cancer up to 10 years]
• Invasive disease free survival (iDFS) [Срок оценки: From date of beginning of hormonotherapy to onset of invasive event, second cancer, or death, up to 10 years.]
• Invasive breast cancer-free survival (iBCFS) [Срок оценки: From date of beginning of hormonotherapy to onset of invasive event or death, up to 10 years.]
• Breast cancer-specific survival (BCSS) [Срок оценки: From date of beginning of hormonotherapy to death from breast cancer, up to 10 years.]
• Overall survival (OS) [Срок оценки: From date of beginning of hormonotherapy to death from any cause, up to 10 years.]
• Quality of life (QoL) questionnaire - Core 30 (QLQ-C30) [Срок оценки: At baseline, 1 year, 2 years, 3 years, 4 years, 5 years]
• Quality of life (QoL) questionnaire - EORTC QLQ-BR23/QLQ-BR45 [Срок оценки: At baseline, 1 year, 2 years, 3 years, 4 years, 5 years]
• Quality of life (QoL) questionnaire - Cancer related fatigue (QLQ-FA12) [Срок оценки: At baseline, 1 year, 2 years, 3 years, 4 years, 5 years]
• Hospital anxiety and depression scale (HADS) [Срок оценки: At baseline, 1 year, 2 years, 3 years, 4 years, 5 years]
• Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) [Срок оценки: At baseline, 1 year, 2 years, 3 years, 4 years, 5 years]
• Impact of Cancer (including fear of recidivism) [Срок оценки: At baseline, 1 year, 2 years, 3 years, 4 years, 5 years]
• Geriatric Core Dataset (G-CODE) [Срок оценки: At baseline, 1 year, 2 years, 3 years, 4 years, 5 years]

Критерии участия

Критерии включения

• 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
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• 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
• M0: Not clinically nor radiologically detectable metastases at time of inclusion
• Primary tumor completely resected and adequate axillary surgery performed, according to current standards
• IHC expression of the estrogen receptor and/or progesterone receptor ≥50%
• HER2 negative according to ASCO criteria in immunohistochemistry and/or genomic analysis (HER2 negativity is defined as IHC 0-1+, or \[IHC 2+ and FISH or CISH nonamplified\])
• No indication of adjuvant chemotherapy
• 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)

• 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

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

Критерии исключения

• Patients who received a neo-adjuvant hormone therapy, a neo-adjuvant or adjuvant chemotherapy or preoperative medical treatment
• Any local or regional recurrence or metastatic disease
• Non-invasive carcinoma
• Bilateral breast cancer (except in case of contralateral DCIS), or history of other invasive ipsi- or contralateral breast cancer
• Patients with a history of another malignancy, except for properly treated cervical carcinoma in situ, and non-melanoma cancer of the skin
• Women with high-risk breast cancer predisposing deleterious germline mutations
• Contra-indications to the administration of anti-aromatase inhibitors
• Patients enrolled in another therapeutic study within 30 days prior to inclusion
• Patients with any other disease or illness, which requires hospitalization or is incompatible with the trial treatment
• 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
• Persons deprived of their liberty or under protective custody or guardianship

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Франция · 2 центра

• Centre Hospitalier Universitaire de Limoges — Limoges
• Institute Gustave Roussy — Villejuif

Идентификаторы

NCT: NCT05297617 · UC-BCG-2103 · 2021-002889-41 · 2024-514480-26-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗