New trial aims to evaluate chemotherapy benefit for ER+/HER2- breast cancer patients

The addition of CDK4/6 inhibitors to endocrine therapy has changed the standard of care for patients with high-risk early-stage estrogen receptor-positive, HER2-negative (ER+/HER2-) breast cancer by reducing the risk of recurrence. However, one patient subgroup continues to present a clinical dilemma. In current practice, patients with low genomic risk but high anatomic risk receive adjuvant chemotherapy because of large tumors or significant nodal involvement, even though their tumors may have lower-risk biology. The ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) has launched the RxFINE-Low (EA1242) trial to determine whether chemotherapy provides additional benefit for this subgroup. 

RxFINE-Low seeks to answer a critical question in breast cancer care, which is: Can patients with high anatomic risk but low genomic risk do similarly well without chemotherapy?" 

Nancy Chan, MD, study chair, medical oncologist, New York University's Perlmutter Cancer Center, NYU Langone

Adjuvant chemotherapy is generally not recommended for postmenopausal patients with earlier-stage ER+/HER2- breast cancer with low Oncotype DX scores and involvement in up to 3 lymph nodes, based on findings from the landmark TAILORx and RxPONDER trials. However, whether it can also be omitted in patients with larger tumors or more extensive nodal involvement has never been evaluated in a large prospective randomized trial. As a result, chemotherapy remains the standard approach for these patients. 

The NATALEE (NCT03701334) and monarchE (NCT03155997) trials established the benefit of adding a CDK4/6 inhibitor to endocrine therapy in high-risk early-stage ER+/HER2- breast cancer. However, most participants had already received chemotherapy before enrollment in those studies. As a result, the incremental benefit of chemotherapy could not be evaluated in those trials. 

RxFINE-Low (EA1242, NCT07391774) is the first prospective randomized phase 3 trial specifically designed to answer this question in patients with high anatomic risk but low genomic risk. The study will enroll nearly 2,000 postmenopausal women and men with high anatomic risk breast cancer, defined as a tumor larger than 5 cm or cancer in more than 3 lymph nodes, and low genomic risk, indicated by an Oncotype DX Breast Recurrence Score® between 0 and 25. 

Participants will be randomized 1:1 to receive either the current approach of adjuvant chemotherapy followed by endocrine therapy plus a CDK4/6 inhibitor (ribociclib) or endocrine therapy plus ribociclib alone. The primary endpoint is invasive breast cancer-free survival. 

"RxFINE-Low will assess whether tumor biology, rather than anatomic tumor burden alone, can guide treatment decisions, and whether chemotherapy can be omitted in some patients," noted Dr. Chan. 

Participants will be followed for up to 10 years to evaluate recurrence, survival, treatment-related side effects, and other study endpoints. Researchers will also collect tumor tissue and blood samples to support future translational research. 

"As treatment options evolve, we need equally rigorous evidence to determine which patients may omit chemotherapy," said Dr. Chan. "RxFINE-Low is designed to provide us with prospective evidence in this space." 

If chemotherapy can be omitted, the findings could spare many patients short- and long-term toxicities. Additionally, the trial results could provide prospective evidence to help inform future coverage decisions. Because genomic testing has not been prospectively validated in patients with high anatomic risk breast cancer, many insurers do not routinely cover Oncotype DX testing for these patients. 

The National Cancer Institute, part of the U.S. National Institutes of Health, is sponsoring the study. ECOG-ACRIN is conducting the trial through the NCI's National Clinical Trials Network (NCTN). Novartis Pharmaceuticals Corporation is providing support to the study through a Cooperative Research and Development Agreement with the NCI. 

For more information about the RxFINE-Low (EA1242) trial, including eligibility criteria and participating sites, visit https://ecog-acrin.org/clinical-trials/ea1242-rxfine-low-breast-cancer.