Single-arm Study to De-escalate Adjuvant Endocrine Therapy Duration in Women With HR+ HER2- Breast Cancer at Very Low Risk of Metastasis
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- UNICANCER
- 入组人数
- 696
- 试验地点
- 3
- 主要终点
- Distant relapse-free interval (DRFI)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 51 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Aromatase inhibitor
Patient will receive standard endocrine therapy (single agent aromatase inhibitors) for a maximum of 2 years.
干预措施: Anti-aromatase inhibitor (Drug)
结局指标
主要结局
Distant relapse-free interval (DRFI)
时间窗: From date of beginning of hormonotherapy to onset of metastases or death, up to 5-years.
Distant relapse-free interval (DRFI) is defined as the time from date of beginning of hormonotherapy to the date of first event of distant recurrence or breast cancer related death
次要结局
- Distant Disease-Free Survival (DDFS)(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)
- Breast cancer-specific survival (BCSS)(From date of beginning of hormonotherapy to death from breast cancer, up to 10 years.)
- Overall survival (OS)(From date of beginning of hormonotherapy to death from any cause, up to 10 years.)
- Evaluate the safety of the treatment in the study population(Throughout study completion, up to 10 years.)
- Invasive disease free survival (iDFS)(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)(From date of beginning of hormonotherapy to onset of invasive event or death, up to 10 years.)
- Quality of life (QoL) questionnaire - Core 30 (QLQ-C30)(At baseline, 1 year, 2 years, 3 years, 4 years, 5 years)
- Quality of life (QoL) questionnaire - EORTC QLQ-BR23/QLQ-BR45(At baseline, 1 year, 2 years, 3 years, 4 years, 5 years)
- Quality of life (QoL) questionnaire - Cancer related fatigue (QLQ-FA12)(At baseline, 1 year, 2 years, 3 years, 4 years, 5 years)
- Hospital anxiety and depression scale (HADS)(At baseline, 1 year, 2 years, 3 years, 4 years, 5 years)
- Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog)(At baseline, 1 year, 2 years, 3 years, 4 years, 5 years)
- Impact of Cancer (including fear of recidivism)(At baseline, 1 year, 2 years, 3 years, 4 years, 5 years)
- Geriatric Core Dataset (G-CODE)(At baseline, 1 year, 2 years, 3 years, 4 years, 5 years)