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

Official title

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

Overview

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.

Detailed description

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.

Interventions

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

Primary outcome measures

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

Secondary outcome measures (12)

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

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• Metastatic cancer

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Canada · 8 centers

• 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

Publications

• 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

Identifiers

NCT: NCT04921137 · REaCT-70

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗