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.

Abstract

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). 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. 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]; <i>P</i> = .034), DDFS (HR, 0.61 [95% CI, 0.38 to 0.98]; <i>P</i> = .040), and OS (HR, 0.39 [95% CI, 0.16 to 0.94]; <i>P</i> = .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% <i>v</i> 37.8%) and thrombocytopenia (4.5% <i>v</i> 0%). Other grade 3 to 4 toxicities were comparable. 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.