BRIGHT-Fe: A phase III randomized trial of intravenous ferric derisomaltose vs low-dose oral iron polypeptide in iron-deficient early breast cancer receiving (neo)adjuvant chemotherapy.

TPS66

Background: Iron deficiency anemia (IDA) is common in early breast cancer (EBC) patients receiving (neo)adjuvant chemotherapy (NACT/ACT) and may contribute to fatigue, transfusion exposure, and reduced chemotherapy dose intensity. Prior randomized trials in mixed malignancies without erythropoiesis-stimulating agents (ESA) showed no clear superiority of intravenous (IV) over oral iron. No adequately powered trial has compared a modern single-infusion high-dose IV strategy with a physiologically titrated low-dose oral regimen in EBC. Methods: BRIGHT-Fe is a Phase III, single-center, open-label, 1:1 randomized superiority trial enrolling 230 women with Stage I–III EBC initiating NACT/ACT and iron deficiency (ferritin <100 ng/mL or 100–300 ng/mL with TSAT <20%) with hemoglobin (Hb) 8.0–11.9 g/dL. Participants are randomized to Arm A: IV ferric derisomaltose 1000 mg (≥50 kg) or 20 mg/kg (<50 kg) as a single infusion before or early in cycle 1. Arm B: Oral iron polypeptide 12–60 mg elemental iron daily using a protocolized titration algorithm. Starting dose is 24 mg/day (two 12 mg capsules once daily). For gastrointestinal intolerance, dose is reduced to 12 mg/day. If Hb rise is <1.0 g/dL by Weeks 2–4, dose is escalated in 12 mg increments up to 60 mg/day. Participants will be randomized 1:1 to Arm A or Arm B, stratified by baseline Hb (<10 vs ≥10 g/dL), menopausal status and platinum use. Stratification factors were selected to maintain balance across clinically relevant subgroups and reduce confounding. The study is powered for overall treatment effect; subgroup analyses are exploratory. The primary endpoint is Hb response at Week 10 (≥2.0 g/dL increase from baseline or Hb ≥12 g/dL). Patients requiring transfusion, ESA rescue or dying before Week 10 are classified as non-responders. Key secondary endpoints include RBC transfusion from randomization to 30 days post-chemotherapy, chemotherapy relative dose intensity (RDI) <85%, mean Hb change and patient-reported fatigue (FACT-An). Safety analyses will include all patients receiving at least one dose of study treatment. Statistical Analysis: Assuming Hb response rates of 30% (IV) vs 10% (oral), 97 patients per arm provide 80% power with two-sided α=0.05. Allowing 15% attrition, total sample size is 230 (115 per arm). The primary analysis follows the intention-to-treat principle using logistic regression adjusted for stratification factors. The treatment effect will be presented as an adjusted odds ratio with 95% confidence intervals. For secondary endpoints appropriate models will be used. These analyses will be exploratory unless multiplicity criteria are satisfied. No formal interim efficacy analysis is planned unless recommended by the Data Safety Monitoring Board. The study is currently open to recruitment. Trial registration: CTRI/2026/02/104238. Clinical trial information: CTRI/2026/02/104238.