NRG-BR007: A phase III trial evaluating de-escalation of breast radiation (DEBRA) following breast-conserving surgery (BCS) of stage 1, HR+, HER2-, RS ≤18 breast cancer.

Julia R. White University of Kansas Medical Center Comprehensive Cancer Center (KUMC CCC), Kansas City, KS info_outline Julia R. White, Reena S. Cecchini, Eleanor Elizabeth Harris, Eleftherios P. Mamounas, Daniel G. Stover, Patricia A. Ganz, Reshma Jagsi, Stewart J. Anderson, Carmen Bergom, Valerie Theberge, Mahmoud El-Tamer, Richard C. Zellars, Dean Alden Shumway, Guang-Pei Chen, Thomas B. Julian, Norman Wolmark, Annabel Goodwin

Authors Julia R. White University of Kansas Medical Center Comprehensive Cancer Center (KUMC CCC), Kansas City, KS info_outline Julia R. White, Reena S. Cecchini, Eleanor Elizabeth Harris, Eleftherios P. Mamounas, Daniel G. Stover, Patricia A. Ganz, Reshma Jagsi, Stewart J. Anderson, Carmen Bergom, Valerie Theberge, Mahmoud El-Tamer, Richard C. Zellars, Dean Alden Shumway, Guang-Pei Chen, Thomas B. Julian, Norman Wolmark, Annabel Goodwin Organizations University of Kansas Medical Center Comprehensive Cancer Center (KUMC CCC), Kansas City, KS, NRG Oncology SDMC, and The University of Pittsburgh, Pittsburgh, PA, St. Luke’s University Health Network, Easton, PA, Orlando Health Cancer Institute, Orlando, FL, Ohio State University Comprehensive Cancer Center, Columbus, OH, UCLA Jonsson Comprehensive Cancer Center, UCLA Fielding School of Public Health, Los Angeles, CA, Emory University School of Medicine, Atlanta, GA, University of Pittsburgh, Pittsburgh, PA, Washington University School of Medicine, St. Louis, MO, CHU de Québec – Université Laval, Québec City, QC, Canada, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical School and Alliance, New York, NY, Indiana University Simon Comprehensive Cancer Center, Indianapolis, IN, Mayo Clinic, Rochester, MN, Medical College of Wisconsin, Milwaukee, WI, The Allegheny Health Network Cancer Institute, Pittsburgh, PA, UPMC Hillman Cancer Center, The University of Pittsburgh School of Medicine, Pittsburgh, PA, Royal Prince Alfred Hospital, Camperdown, Australia Abstract Disclosures Research Funding U.S. National Institutes of Health U.S. National Institutes of Health. Background: Approximately 50% of newly diagnosed invasive breast cancers are stage 1, with the majority being ER/PR-positive, HER2-negative. Genomic assays such as the Oncotype DX have identified patients (pts) with reduced risk of distant metastasis and without benefit from chemotherapy added to endocrine therapy, freeing them from excess toxicity. Genomic assays are also recognized as prognostic for in-breast recurrence (IBR) after BCS and could similarly allow de-escalation of adjuvant radiotherapy (RT). Reducing overtreatment is of interest to pts, providers, and payers. Methods: We hypothesize that BCS alone is non-inferior to BCS plus RT for in-breast recurrence and breast preservation in women intending endocrine therapy (ET) for stage 1 invasive breast cancer (ER &/or PR positive, HER2-negative with an Oncotype DX Recurrence Score [RS] of ≤18). Stratification is by age (<60; ≥60), tumor size (≤1 cm; >1-2cm), and RS (<11, 11-18). Pts are randomized post-BCS to Arm 1 with breast RT using standard methods (hypo- or conventional-fractionated whole breast RT with/without boost, or APBI) with ≥5 yrs of ET (tamoxifen or AI) or Arm 2 with ≥5 yrs of ET (tamoxifen or AI) alone. The specific regimen of ET in both arms is at the treating physician’s discretion. Eligible pts are stage 1: pT1 (≤2 cm), pN0, age ≥50 to <70 yrs, s/p BCS with negative margins (no ink on tumor), s/p axillary nodal staging (SNB or ALND), ER &/or PR positive (ASCO/CAP), HER2-negative (ASCO/CAP), and Oncotype DX RS of ≤18 (diagnostic core biopsy or resected specimen). Primary endpoint is in-breast recurrence (invasive breast cancer or DCIS). Secondary endpoints are breast conservation rate, invasive in-breast recurrence, relapse-free interval, distant disease-free survival, overall survival, patient-reported breast pain, patient-reported worry about recurrence, and adherence to ET. We assume a clinically acceptable difference in IBR of 4% at 10 yrs to judge omission of RT as non-inferior (10-yr event-free survival for RT group is 95.6% vs 91.6% for the omission of RT group). BR007 is powered to detect non-inferiority with 80% power and a one-sided α=0.025, assuming that there would be a ramp-up in accrual in the first two years (leveling off in Yrs 3-5); 1,670 pts (835 per arm) are required for randomization. Conservative loss to follow-up is 1% per yr. Some of the T1a pts screened may have Oncotype DX scores >18, making them ineligible for the study. In the accrual process, 1,714 pts will be required to register to ensure that our final randomized cohort is 1,670 pts. Current accrual (02-08-2023) is 370 screened and 323 randomized (~87% of predicted accrual). Clinical trial information: NCT04852887.

Clinical