December 05 2023
PITTSBURGH, PA — Opened to patient enrollment earlier this year, NRG Oncology’s NRG-BR008 clinical trial (The “HERO” Study) is a large, randomized study that is comparing the recurrence-free interval (RFI) among patients with early-stage, low risk, HER2-positive breast cancer who undergo breast conserving surgery and receive HER2-directed therapy and are randomized to receive adjuvant breast radiotherapy per the current standard of care or forego breast radiotherapy.
Given that radiotherapy is known to roughly halve local recurrence rates following lumpectomy in many settings, it is hypothesized that local recurrences may increase modestly with the omission of radiotherapy in the proposed populations (pT1N0 for those receiving adjuvant chemotherapy and, clinically T ≤3 cm N0 at baseline and ypT0N0 after neoadjuvant therapy for those receiving neoadjuvant chemotherapy).
However, it is anticipated that this small rise in local recurrences will not be associated with regional or distant recurrences and that breast-cancer-specific survival events will not increase significantly. As a result, it is hypothesized that the RFI without radiotherapy will not decrease to a clinically significant extent (a 3.6% difference between study arms in composite RFI events is the maximum that will be tolerated in the study; in other words, a reduction in 7-year RFI from 97.5% with RT to 93.9% without RT will be the maximum acceptable decrement).
Secondary objectives include estimating the 7-year cumulative incidence of ipsilateral breast recurrence (IBR) for the radiation-omitting arm and testing the hypothesis that the 7-year IBR rate is <7% for patients not receiving radiation therapy; estimating the time to ipsilateral breast recurrence (IBR) by treatment arm; determining the time to local regional recurrence (LRR), disease-free survival (DFS), and overall survival (OS) by treatment arm; and evaluating whether there is a difference in patient-reported breast pain and worry about recurrence in patients who do or do not receive radiation.
“Studying the omission of radiotherapy among this population of HER2+ breast cancer patients who are understood to have excellent outcomes will enable them to weigh the attendant inconveniences, cost, and morbidity of radiotherapy in light of an established absolute benefit of radiotherapy, which may prove to be modest” stated Lior Braunstein, MD, of Memorial Sloan Kettering and lead investigator for the NRG-BR008/HERO trial.
Melissa Mitchell, MD, of MD Anderson Cancer Center, and co-principal investigator of the study states, “In the era of HER2-targeted therapy, local and distant recurrence rates for early stage HER2-positive breast cancer are arguably lower than the most favorable cohorts of hormone positive breast cancer, for which we have already established minimal impact of radiotherapy. It is essential that we also question the use of radiotherapy in this newly established favorable risk population.”
Watch the NRG-BR008 "HERO" Study Interview with PI Dr. Braunstein on YouTube
Supported by grants U10CA180868 (NRG Operations), U10CA180822 (SDMC), from the National Cancer Institute (NCI), part of the National Institutes of Health and conducted by the NCI National Clinical Trials Network.
About NRG Oncology
NRG Oncology conducts practice-changing, multi-institutional clinical and translational research to improve the lives of patients with cancer. Founded in 2012, NRG Oncology is a Pennsylvania-based nonprofit corporation that integrates the research of the legacy National Surgical Adjuvant Breast and Bowel Project (NSABP), Radiation Therapy Oncology Group (RTOG), and Gynecologic Oncology Group (GOG) programs. The research network seeks to carry out clinical trials with emphases on gender-specific malignancies, including gynecologic, breast, and prostate cancers, and on localized or locally advanced cancers of all types. NRG Oncology’s extensive research organization comprises multidisciplinary investigators, including medical oncologists, radiation oncologists, surgeons, physicists, pathologists, and statisticians, and encompasses more than 1,300 research sites located world-wide with predominance in the United States and Canada. NRG Oncology is supported primarily through grants from the National Cancer Institute (NCI) and is one of five research groups in the NCI’s National Clinical Trials Network.