October 17 2023
NRG-BR009 (“OFSET”): A Phase III Adjuvant Trial Evaluating the Addition of Adjuvant Chemotherapy to Ovarian Function Suppression and Endocrine Therapy in Premenopausal Patients with pN0-1, ER-Positive/HER2-Negative Breast Cancer and an Oncotype Recurrence Score of ≤ 25
Recently activated & now enrolling patients!
Written by Shannon Puhalla, MD; NRG-BR009 Protocol Officer
The NRG-BR009 (“OFSET”) trial will be evaluating whether adjuvant chemotherapy added to ovarian function suppression and endocrine therapy is superior to ovarian function suppression and endocrine therapy alone in improving invasive breast cancer-free survival (IBCFS) among premenopausal, early-stage breast cancer patients with ER-positive, HER2-negative tumors and a 21-gene recurrence score between 16-25 (for pN0 patients) and 0-25 (for pN1 patients). This study will answer a decades old question regarding the benefit of chemotherapy, whether from cytotoxic effects or ovarian suppressive effects. The recurrence score was initially developed from the samples in NSABP legacy studies, B-14 and B-20 and has changed the way that women with early stage ER+ breast cancers are treated, allowing many to safely omit chemotherapy. The TAILORx and RxPONDER trials examined this assay in a prospective randomized fashion, and confirmed that many women with early stage breast cancer can avoid chemotherapy; however, the data were less clear in premenopausal women. BR009 is the next logical and needed study to definitively determine if young women with these specific recurrence scores benefit from chemotherapy.
This study, now CIRB approved, will enroll a total of 3960 women. The primary endpoint is invasive breast cancer free survival. Key secondary endpoints include overall survival, distant recurrence free interval and an evaluation of patient reported outcomes and quality of life led by Patti Ganz, MD. Chemotherapy and ovarian function suppression have unique challenges in young women including not only menopausal symptom burden but also influences fertility and family planning.
The study is pragmatic and the therapy options include standard of care commonly used chemotherapy regimens in those patients randomized to chemotherapy and with ovarian suppression, there is freedom in agent used and dosing schedule. The assessments of adverse events are particularly focused on those side effects seen with estrogen deprivation. Monitoring of estradiol levels is recommended to assure optimal ovarian function suppression. Protocol officer, Shannon Puhalla, MD from the UPMC Hillman Caner Center is enthusiastic about the study and its potential impact. “OFSET/BR009 will answer important questions in young women, is chemo needed, who does it benefit and at what cost with potential side effects?”.
- Watch for our interview with Dr. Terry Mamounas (NRG-BR009 principal investigator) and Dr. Shannon Puhalla (NRG-BR009 protocol officer) in an upcoming newsletter.
- The Patient Study Web Page and Patient Brochure for NRG-BR009 are now available on the NRG website