Abstract RF2-04: Effect of adjuvant carboplatin intensified chemotherapy versus standard chemotherapy on survival in women with high-risk early-stage triple-negative breast cancer (CITRINE): a phase 3 randomized trial

Abstract Background: The benefit of incorporating carboplatin into adjuvant anthracycline/taxane-based chemotherapy in triple-negative breast cancer (TNBC) remains controversial. This study aimed to evaluate the efficacy and safety of epirubicin and cyclophosphamide followed by weekly paclitaxel with or without carboplatin as adjuvant therapy for patients with high-risk early-stage TNBC. Methods: This open-label, randomized, phase 3 trial was conducted in China. Female patients with operable high-risk TNBC (defined as either regional node-positive or node-negative with a Ki-67 labeling index of ≥50%) after definitive surgery were randomized in a 1:1 ratio into either the carboplatin group (two-week epirubicin and cyclophosphamide followed by weekly paclitaxel combined with carboplatin) or the control group (three-week or two-week epirubicin and cyclophosphamide followed by weekly paclitaxel). The primary endpoint was disease-free survival (DFS) in the intention-to-treat population. Second endpoints included recurrence-free survival (RFS), distant disease-free survival (D-DFS), overall survival (OS) and safety. Results: Of the 808 enrolled patients, 807 received study treatment. At a median follow-up of 44.7 months, the three-year DFS rate was 92.3% in the carboplatin group and 85.8% in the control (hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.43 to 0.95; P=0.026). For secondary endpoints, the carboplatin group was associated with superior outcomes in three-year RFS (93.8% vs. 88.3%; HR, 0.59; 95% CI 0.37 to 0.93; P = 0.021), three-year D-DFS (94.8% vs 89.8%; HR, 0.61; 95% CI 0.37 to 0.98; P = 0.039), and three-year OS (98.0% vs 94.0%; HR, 0.41; 95% CI 0.20 to 0.83; P = 0.011). Exploratory forest plot analyses for DFS in the ITT population showed HRs that consistently favored the carboplatin group. The incidence of grade 3-4 treatment related adverse events were 66.7% (269/403) for the carboplatin group and 55% (222/404) for the control group. No treatment related deaths occurred. Conclusions: The addition of carboplatin to adjuvant anthracycline/taxane-based chemotherapy significantly improves survival outcomes with manageable toxicity in patients with high-risk early-stage TNBC. Trial registration number: ClinicalTrials.gov (NCT04296175). Citation Format: Y. Liu, Y. Gong, X. Zhu, G. Liu, K. Yu, F. Yang, L. Chen, M. He, Z. Hu, C. Chen, A. Cao, J. Li, Y. Hou, G. Di, J. Wu, Y. Jiang, L. Fan, Z. Wang, Z. Shao, . Effect of adjuvant carboplatin intensified chemotherapy versus standard chemotherapy on survival in women with high-risk early-stage triple-negative breast cancer (CITRINE): a phase 3 randomized trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr RF2-04.