Evaluating Harms and Benefits of Endocrine Therapy in Patients ≥70 Years of Age With Lower Risk Breast Cancer

Официальное название

A Randomised, Multicentre Trial Evaluating Harms and Benefits of Endocrine Therapy in Patients ≥70 Years of Age With Lower Risk Breast Cancer (REaCT-70)

Обзор

The current standard of care for stage 1 hormone receptor-positive (HR+) breast cancer consists of breast-conserving surgery followed by adjuvant radiotherapy (RT) and endocrine therapy (ET) for at least 5 years. The benefit of adjuvant ET for older patients is mitigated because of their increase risk of death from other causes and shorter time horizon to live. Clinical and pathological factors such as low-intermediate grade, tumor size ≤2 cm, and older age have been used in a few studies to identify patients with a lower risk of recurrence that might benefit from adjuvant therapy de-escalation, i.e. omission of RT or ET. Since there is no dedicated randomized clinical trial (RCT) conducted to evaluate the omission of ET, there is clinical equipoise as to whether we can omit adjuvant ET in older patients with lower-risk early-stage breast cancer. Therefore, we propose a randomised, multicentre trial evaluating harms and benefits of endocrine therapy in patients ≥70 years of age with lower risk breast cancer.

Подробное описание

The current standard of care for stage 1 hormone receptor-positive (HR+) breast cancer consists of breast-conserving surgery followed by adjuvant radiotherapy (RT) and endocrine therapy (ET) for at least 5 years. The benefit of adjuvant ET for older patients is mitigated because of their increase risk of death from other causes and shorter time horizon to live. This population is also more likely to have additional comorbidities which can lead to higher treatment-related adverse events impacting quality of life and precipitating functional decline. Clinical and pathological factors such as low-intermediate grade, tumor size ≤2 cm, and older age have been used in a few studies to identify patients with a lower risk of recurrence that might benefit from adjuvant therapy de-escalation, i.e. omission of RT or ET. The body of evidence from small prospective studies, mathematical modelling study and retrospective analyses would suggest that the omission of ET in older patients with favourable HR+ breast cancer who had optimal local therapy (i.e. breast conserving surgery followed by adjuvant radiotherapy) does not compromise locoregional and survival outcomes. Since there is no dedicated randomized clinical trial (RCT) conducted to evaluate the omission of ET, there is clinical equipoise as to whether we can omit adjuvant ET in older patients with lower-risk early-stage breast cancer. Therefore, we propose a randomised, multicentre trial evaluating harms and benefits of endocrine therapy in patients ≥70 years of age with lower risk breast cancer.

Вмешательства

• Другое No endocrine therapy
  No endocrine therapy given
• Другое Endocrine therapy
  Endocrine therapy given for at least 5 years

Первичные конечные точки

• Hierarchical composite endpoint (OS, iDFS, MDFS, QoL) [Срок оценки: 5 years]

Вторичные конечные точки (12)

• Overall survival [Срок оценки: 5 years]
• Invasive disease free survival [Срок оценки: 5 years]
• Metastatic disease free survival [Срок оценки: 5 years]
• Health-related quality of life: FACT-B plus ES [Срок оценки: Baseline, 26-weeks, 1-year, 2-years, 3-years, 4-years, 5-years]
• Hot flashes [Срок оценки: Baseline, 26-weeks, 1-year, 2-years, 3-years, 4-years, 5-years]
• Joint pain [Срок оценки: Baseline, 26-weeks, 1-year, 2-years, 3-years, 4-years, 5-years]
• Health-related quality of life: FACT-G [Срок оценки: Baseline, 26-weeks, 1-year, 2-years, 3-years, 4-years, 5-years]
• Health-related quality of life: EQ-5D-5L [Срок оценки: Baseline, 26-weeks, 1-year, 2-years, 3-years, 4-years, 5-years]
• Breast Cancer Specific Survival [Срок оценки: 5 years]
• Adverse events of interest [Срок оценки: 5 years]
• Change in geriatric domains [Срок оценки: Baseline, 1 year, 5 years]
• Adherence with prescribed endocrine therapy [Срок оценки: 26-weeks, 1-year, 2-years, 3-years, 4-years, 5-years]

Критерии участия

Критерии включения

• New invasive estrogen and/or progesterone receptor-positive (ER+ and/or PR+), HER2-negative (HER2-) invasive breast carcinoma diagnosis as per ASCO-CAP guidelines
• The primary tumour characteristics are either: Grade 1 and ≤3 cm on microscope exam, OR Grade 2 and ≤2 cm on microscope exam, OR Grade 3 and ≤1 cm on microscope exam
• Treated with standard loco-regional therapy: breast conserving surgery followed by adjuvant radiotherapy OR total mastectomy
• Axillary node-negative (cN0 or pN0)
• Able to provide oral consent and complete questionnaires in French or English as per study protocol

Критерии исключения

• Metastatic cancer

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Канада · 8 центров

• Cross Cancer Institute — Edmonton
• Waterloo Regional Health Network — Kitchener
• London Health Sciences Centre — London
• Oak Valley Health — Markham
• The Ottawa Hospital — Ottawa
• Thunder Bay Regional Health Sciences Centre — Thunder Bay
• Allan Blair Cancer Centre — Regina
• Saskatoon Cancer Centre — Saskatoon

Публикации

• Savard MF, Clemons M, Hutton B, Jemaan Alzahrani M, Caudrelier JM, Vandermeer L, Liu M, Saunders D, Sienkiewicz M, Stober C, Cole K, Shorr R, Arnaout A, Chang L. De-escalating adjuvant therapies in older patients with lower risk estrogen receptor-positive breast cancer treated with breast-conserving surgery: A systematic review and meta-analysis. Cancer Treat Rev. 2021 Sep;99:102254. doi: 10.1016/ PMID 34242928
• Alzahrani M, Clemons M, Chang L, Vendermeer L, Arnaout A, Larocque G, Cole K, Hsu T, Saunders D, Savard MF. Management Strategies for Older Patients with Low-Risk Early-Stage Breast Cancer: A Physician Survey. Curr Oncol. 2021 Dec 21;29(1):1-13. doi: 10.3390/curroncol29010001. PMID 35049675
• Savard MF, Alzahrani MJ, Saunders D, Chang L, Arnaout A, Ng TL, Brackstone M, Vandermeer L, Hsu T, Awan AA, Cole K, Larocque G, Clemons M. Experiences and Perceptions of Older Adults with Lower-Risk Hormone Receptor-Positive Breast Cancer about Adjuvant Radiotherapy and Endocrine Therapy: A Patient Survey. Curr Oncol. 2021 Dec 8;28(6):5215-5226. doi: 10.3390/curroncol28060436. PMID 34940075

Идентификаторы

NCT: NCT04921137 · REaCT-70

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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