Adjuvant Epirubicin Plus Cyclophosphamide Followed by Taxanes With or Without Carboplatin in Early-Stage Triple-Negative Breast Cancer (RJBC 1501): A Randomized Phase III Trial
Xiaosong Chen, Jiahui Huang, Haoting Shi, Juanying Zhu, Weizhu Wu, Guolin Ye, Qi He, Yong Shi, Anqin Zhang, Xiaohong Xie, Xiaodong Wang, Xiangjing Chen, Wei-Li Wu, Jundong Wu, Zhian Li, Zhanwen Li, Yuechu Dai, Weili Ren, Qing Shao, Yongan Chen, Yong Zeng, Fengzhe Zhang, Shuwen Dong, Mark D. Pegram, Kunwei Shen
Abstract
PURPOSE To evaluate the efficacy and safety of adjuvant epirubicin plus cyclophosphamide followed by taxanes (EC-T) versus EC-T plus carboplatin (EC-TCb) in patients with early-stage triple-negative breast cancer (TNBC). PATIENTS AND METHODS In this phase III trial, patients with TNBC with node-positive or node-negative (tumor size ≥1.0 cm) disease who received definitive surgery, were stratified by lymph node status and randomly assigned in a 1:1 ratio to receive four cycles of EC followed by four cycles T with or without carboplatin adjuvant chemotherapy. The primary end point was disease-free survival (DFS). Secondary end points included distant DFS (DDFS), overall survival (OS), and safety. This study had 80% power to detect a DFS hazard ratio (HR) of 0.64, with a two-sided type I error of 0.05. RESULTS A total of 786 patients were randomly assigned to receive EC-T (n = 391) or EC-TCb (n = 395) between March 2016 and March 2023. With a median follow-up of 4.52 (IQR, 2.83-6.06) years, 62 and 41 events were reported in the EC-T and EC-TCb arm, respectively. Adding carboplatin significantly improved DFS (HR, 0.66; [95% CI, 0.44 to 0.97]; P = .034), DDFS (HR, 0.61 [95% CI, 0.38 to 0.98]; P = .040), and OS (HR, 0.39 [95% CI, 0.16 to 0.94]; P = .029). Grade 3 to 4 adverse events were more frequent among the EC-TCb arm (49.9%) than the EC-T arm (38.7%), primarily driven by higher incidence of neutropenia (47.0% v 37.8%) and thrombocytopenia (4.5% v 0%). Other grade 3 to 4 toxicities were comparable. CONCLUSION Adding carboplatin to adjuvant EC-T chemotherapy significantly improves DFS, DDFS, and OS in patients with early-stage TNBC. Although increased hematologic toxicity was observed, no new safety signals emerged.