OT1-03-01: A Randomized Phase III Clinical Trial of Standard Adjuvant Endocrine Therapy +/− Chemotherapy in Patients (pts) with 1–3 Positive Nodes, Hormone Receptor (HR)-Positive and HER2−Negative Breast Cancer with Recurrence Score (RS) of 25 or Less: SWOG S1007.

Abstract

Background Multi-gene tumor assays have provided clinically useful prognostic information for pts with HR receptor and node-positive breast cancer. The 21-gene RS was shown to be prognostic for pts treated with tamoxifen alone, and exploratory studies suggested that it may be predictive of benefit from chemotherapy. In retrospective analyses from SWOG S8814, pts with low RS appeared to get no benefit from adjuvant CAF chemotherapy, while those with higher RS did. These retrospective data require validation, especially since more modern chemotherapy might be more effective than the regimen used in S8814. Specific Aims/Trial Design: In January 2011, SWOG activated a phase III randomized clinical trial (registration number NCT01272037) to test the efficacy of using modern chemotherapy regimens in node positive pts with low RS, whose prognosis is still moderately poor but may not benefit from adjuvant chemotherapy based on tumor biology predicted by the RS value. The trial is similar to the Tailor RX study, but focuses on a node-positive population with low and intermediate RS. Eligibility Criteria: Pts with 1 to 3 positive lymph nodes, HR-positive and HER2−negative invasive breast cancer with RS ≤ 25 are eligible for randomization. Pts will be informed of their RS. Target and Present Accrual: Approximately 9400 patients will be screened to randomize 4000, stratified by RS (0-13 vs. 14–25), menopausal status, and axillary surgery (sentinel node vs. complete dissection); 46 are presently registered. Statistical Methods: The trial is powered to find a significant interaction of treatment assignment and the continuous RS value and, subsequently, derive a cut point for using the assay to guide treatment decisions. Pts who consent to screening are required to consent to banking of the tumor tissue and blood for further studies. Patient Reported Outcomes will be collected pre, post-screening and post-randomization. The study also has a cost-effectiveness analysis. Funding: Supported in part by National Cancer Institute grants CA32102 & CA38926, and in part by the Susan G. Komen for the Cure® Research Program, and the Breast Cancer Research Foundation. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT1-03-01.

Biomarker assessment and molecular testing for prognostication in breast cancer

“…In the RxPONDER trial, women with one to three positive lymph nodes, and a RS ≤25 will be randomized to hormonal therapy alone versus chemotherapy plus hormones. The study is currently recruiting participants …”

Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100 000 women in 123 randomised trials

“…We could not test such hypotheses. Three new trials (MINDACT, 35 TAILORx, 36 RxPONDER 37 ) have included more than 10 000 patients with ER-positive disease and measurements of gene expression profile who have been randomly allocated chemoendocrine therapy versus the same endocrine therapy alone. Their combined results will be able to assess reliably the prognostic relevance of such measurements (and of other measurements, including quantitative immunohistochemistry 30 ) and will help to assess any differences in chemotherapy RRs between subgroups.…”

The 21-Gene Recurrence Score and Locoregional Recurrence in Breast Cancer Patients

“…1 Additionally, the ongoing RxPonder trial (Rx for Positive Node, Endocrine Responsive breast cancer; clinical trial registry NCT01272037) is using an RS > 25 to define high-risk patients. 17 For this study, we therefore chose a pre-defined RS > 25 as a clinically relevant cut-off to determine a group of patients at high enough risk of LRR to perhaps warrant more aggressive local therapy.…”