Phase 3 RxFINE-Low: ribociclib CDK4/6 inhibitor guided by Oncotype DX genomic risk

This National Cancer Institute–sponsored, randomized Phase 3 trial tests whether patients with high anatomic-stage ER-positive/HER2-negative breast cancer but low genomic recurrence risk (Oncotype DX Recurrence Score 0–25) can safely omit adjuvant chemotherapy. Arm A receives physician’s choice standard chemotherapy first, then endocrine therapy (letrozole, anastrozole, or exemestane; aromatase inhibitors that suppress estrogen production) plus ribociclib (Novartis; a CDK4/6 inhibitor that blocks cell-cycle progression through the cyclin D–CDK4/6–RB pathway). Arm B skips chemotherapy and receives endocrine therapy plus ribociclib up front. The key commercial/scientific angle is “de-escalation” in biologically favorable disease: if endocrine therapy + CDK4/6 inhibition is non-inferior to chemo-containing therapy, it could reduce chemo exposure in a subset defined by genomic testing. Today’s care for higher-stage HR+/HER2− disease often includes surgery and radiation as appropriate, plus multi-year endocrine therapy, with chemotherapy commonly used for higher-risk clinicopathologic features; CDK4/6 inhibition has become an important adjuvant option in selected higher-risk patients, and this trial asks whether genomics can refine who truly needs chemo.