Dose-Dense Paclitaxel Plus Carboplatin (PCdd) versus Epirubicin and Cyclophosphamide (ECdd) Followed by Paclitaxel (P) As Adjuvant Chemotherapy in Early Triple-Negative Breast Cancer at High Risk of Recurrence, A Randomised, Open-Label, Phase 3 Trial

Background: Triple-negative breast cancer (TNBC) may be more sensitive to platinum-based regimens. This open-label, randomized phase III trial aimed to compare dose dense paclitaxel plus carboplatin (PCdd) with dose-dense epirubicin and cyclophosphamide followed by paclitaxel (ECdd-P) regimen as adjuvant chemotherapy (AC) for high-risk early TNBC. Methods: We included Chinese patients with high recurrence risk TNBC who underwent primary breast surgery. They were randomly assigned in a 1:1 ratio to receive PCdd (paclitaxel 150 mg/m2 on day 1 and carboplatin AUC=3 on day 2 for 8 cycles) or ECdd-P (epirubicin 80 mg/m2 divided in 2 days and cyclophosphamide 600 mg/m2 on day 1 for 4 cycles followed by paclitaxel 175 mg/m2 on day 1 for 4 cycles) every 2 weeks, with granulocyte colony-stimulating factor (G-CSF) support. The primary endpoint was 3-year disease-free survival (DFS); the secondary endpoints were overall survival (OS) and safety. Findings: The intent-to-treat population included 143 patients (70 in the PCdd arm and 73 in the ECdd-P arm). Compared with the ECdd-P arm, the PCdd arm had significantly higher 3-year DFS (93⋅9% vs.79⋅1%, hazard ratio[HR]=3⋅224, 95% confidence interval [CI] =1⋅420-7⋅321, log-rank p=0⋅0051) and OS (98⋅5% vs.92⋅9% [HR] =7⋅092, 95% CI=1⋅212-16⋅630, log-rank p=0⋅0281). The 3-year DFS in the PCdd arm was significantly higher (p 40 years, Ki-67>30, and clinically evaluated lymph nodes. Both regimens were well tolerated. Worse neutropenia (grade 3/4) was found in the ECdd-P arm (47⋅9% vs. 21⋅4%, p=0⋅001). Interpretation: PCdd was superior to ECdd-P as AC for early TNBC with respect to improving the 3-year DFS and OS. PCdd also yields lower hematological toxicity.Thus, PCdd might be a preferred AC regimen for early TNBC patients with high recurrence risk. Trial Registration: This trial is registered at ClinicalTrials. gov (number NCT01378533). Funding Statement: This study was supported by National Key Research and Development Program of China (2018YFC1312101); and Chinese Academy of Medical Science Initiative funded this study for Innovative Medicine (CAMS-12M-1-010). Declaration of Interests: All authors declare no conflicts of interest. Ethics Approval Statement: All interventions were performed in accordance with Chinese laws and regulations and the Helsinki declaration. The study protocol was approved by the independent ethics board committee at the National Cancer Center, Chinese Academy of Medical Sciences (Approval number: CH-BC-012).