Abstract P3-18-04: Evaluating de-escalation of breast radiation (DEBRA) following lumpectomy for breast conservative treatment of stage 1, hr+, HER2-, RS ≤18 breast cancer: NRG-BR007 a phase III trial

Roughly 50% of newly diagnosed breast cancer is stage 1, the majority being ER/PR positive, HER2- negative. Genomic assays such as Oncotype DX® have identified patients with reduced distant metastasis and lack of chemotherapy benefit, allowing patients to avoid excess toxicity. These genomic assays have been shown to be prognostic for local-regional recurrence (LRR). The de-escalation of therapy is of interest to patients, providers, and payers. Low risk, as identified by both the use of Oncotype and Mammaprint® is associated with low LRR after lumpectomy and breast radiotherapy. TRIAL DESIGN: In the DEBRA trial, we hypothesized that breast-conserving surgery (BCS) alone is non-inferior to BCS plus radiotherapy for in-breast cancer control and breast preservation in women intending appropriate endocrine therapy for stage 1 (ER and/or PR-positive, HER2-negative, and Oncotype DX Recurrence Score [RS] low) breast cancer. Stratification is by age (<60; ≥60), tumor size (≤1 cm; >1-2 cm), and RS <11, RS 11-18. Patients are randomized to either breast radiotherapy (RT) plus endocrine therapy (arm 1) or to observation and endocrine therapy (arm 2). Arm 1 therapy is post-lumpectomy breast RT using standard methods (hypo- or conventional-fractionated whole breast irradiation with or without boost, accelerated partial breast irradiation) and at least 5 years of endocrine therapy (tamoxifen or aromatase inhibitor). In arm 2, at least 5 years of endocrine therapy (tamoxifen or aromatase inhibitor) will be given. The specific regimen of endocrine therapy in both arms is at the treating physician’s discretion. ELIGIBLITY: Patients who are stage 1: pT1 (2 cm), pN0, age ≥50 to <70 years, status post (s/p) lumpectomy with negative margins (no ink on tumor ), s/p axillary nodal staging (SNB or AND), ER and/or PR positive by ASCO/CAP, HER2-negative by ASCO/CAP, and Oncotype DX RS of ≤18 on diagnostic core biopsy or resected specimen. ENDPOINTS: Primary: In-breast recurrence (IBR). Secondary: Breast conservation rate, invasive in-breast recurrence (IIBR), relapse free interval (RFI), distant disease-free survival (DDFS), overall survival (OS), patient-reported breast pain, patient-reported worry about recurrence, and adherence to endocrine therapy. STATISTICS: We assume a clinically acceptable difference in IBR of 4% at 10 years to judge omission of RT as non-inferior (10-year event-free survival for RT group is 95.6% versus 91.6% for the omission of RT group). To be able to detect non-inferiority with 80% power and a one sided α=0.025, and assuming that there would be a ramp-up in accrual in the first two years of the study (leveling off in Years 3-5), 1,670 (835 per arm) patients are required to be randomized. This conservatively assumes loss to follow-up will be 1% per year. Some of the T1a patients accrued to this study will have oncotype DX scores >18, making them ineligible for the study. An extra step in the accrual process will require us to register 1,714 patients to ensure our final randomized cohort is 1,670 patients. Accrual: Screen 1,714 to randomize 1,670 into the study. Contact information: Protocol: CTSU member website: https://www.ctsu.org. NRG Oncology Pgh Clinical Coordinating Dpt: 1-800-477-7227 or ccd@nsabp.org. Support: U10CA180868, U10CA180822. NCT04852887. Citation Format: Julia White, Stewart J Anderson, Eleanor ER Harris, Eleftherios P Mamounas, Daniel G Stover, Patricia A Ganz, Reshma Jagsi, Reena S Cecchini, Carmen Bergom, Valerie Theberge, Mahmoud El-Tamer, Rich C Zellars, Dean A Shumway, Guang-Pei Chen, Thomas B Julian, Norman Wolmark. Evaluating de-escalation of breast radiation (DEBRA) following lumpectomy for breast conservative treatment of stage 1, hr+, HER2-, RS ≤18 breast cancer: NRG-BR007 a phase III trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-18-04.