A Phase III, Randomized Clinical Trial of Standard Adjuvant Endocrine Therapy +/- Chemotherapy in Patients With 1-3 Positive Nodes, Hormone Receptor-Positive and HER2-Negative Breast Cancer With Recurrence Score (RS) of 25 or Less. RxPONDER: A Clinical Trial Rx for Positive Node, Endocrine Responsive Breast Cancer
This randomized phase III clinical trial studies how well tamoxifen citrate, anastrozole,
letrozole, or exemestane with or without chemotherapy work in treating patients with breast
cancer that has spread from where it began in the breast to surrounding normal tissue
(invasive). Estrogen can cause the growth of breast cancer cells. Hormone therapy, using
tamoxifen citrate, may fight breast cancer by blocking the use of estrogen by the tumour
cells. Aromatase inhibitors, such as anastrozole, letrozole, and exemestane, may fight
breast cancer by lowering the amount of estrogen the body makes. Drugs used in chemotherapy
work in different ways to stop the growth of tumour cells, either by killing the cells, by
stopping them from dividing, or by stopping them from spreading. It is not yet known whether
giving tamoxifen citrate, anastrozole, letrozole, or exemestane is more effective with
combination chemotherapy in treating patients with breast cancer.
- RS, as measured by Oncotype DX
- Local disease-free interval
- Toxicities using standard National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.0
I. To determine the effect of chemotherapy in patients with node positive breast cancer who
do not have high recurrence scores (RS) by Oncotype DX.
I. To compare overall survival (OS), distant disease-free survival (DDFS) and local
disease-free interval (LDFI) by receipt of chemotherapy or not and its interaction with RS.
II. To compare the toxicity across the treatment arms. III. To perform other assays or tests
(in particular the prediction analysis of microarray [PAM50] risk of relapse score), as they
are developed and validated that measure potential benefit of chemotherapy and compare them
to Oncotype DX.
IV. To determine the impact of management with Oncotype DX on patient-reported anxiety
(co-primary Health-Related Quality of Life [HRQL] outcome) prior to screening, after
disclosure of test results, and during the randomized trial.
V. To determine the impact of Oncotype DX on the initial management cost of node-positive,
hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative
VI. To compare patient-reported utilities (e.g., quality of life [QOL]) for those randomized
to chemotherapy versus no chemotherapy.
VII. Using modeling and DFS information from the trial, to estimate the cost-effectiveness
of management with Oncotype DX vs usual care.
VIII. To determine the role of other assays (e.g., PAM50) as predictors of DFS, DDFS, and
LDFI for patients randomized to chemotherapy versus no chemotherapy.
IX. To determine the impact of treatment with chemotherapy versus no chemotherapy on
patient-reported fatigue and cognitive concerns (secondary HRQL outcomes).
X. To determine the impact of management with Oncotype DX on patient-reported decision
conflict, perceptions regarding Oncotype DX testing, and survivor concerns prior to
screening, after disclosure of test results, and during the randomized trial (secondary HRQL
Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive a protocol-approved chemotherapy regimen based on the patient and/or
physician preference. Patients then receive a protocol-approved adjuvant endocrine therapy
comprising tamoxifen citrate, an aromatase inhibitor (anastrozole, letrozole, or
exemestane), or both for 5-10 years in the absence of disease progression or unacceptable
ARM II: Patients receive a protocol-approved endocrine therapy comprising tamoxifen citrate,
an aromatase inhibitor (anastrozole, letrozole, or exemestane), or both for 5-10 years in
the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year,
every 6 months for 4 years, and then yearly for 15 years.
View this trial on ClinicalTrials.gov