Phase 3 trial of adjuvant carboplatin intensified chemotherapy versus standard chemotherapy for high risk early stage TNBC

The phase 3 CITRINE trial, at Fudan University Shanghai Cancer Center in China, evaluated epirubicin and cyclophosphamide followed by weekly paclitaxel with or without carboplatin as adjuvant therapy for high risk, early stage, triple negative breast cancer (TNBC). The trial included 807 female patients with operable TNBC (either regional node positive or node negative with Ki-67 labelling index of ≥ 50%). Patients were randomized 1:1 to the carboplatin arm (four cycles of two weekly epirubicin and cyclophosphamide followed by four cycles of weekly paclitaxel combined with carboplatin) or the control arm (four cycles of three or two weekly epirubicin and cyclophosphamide followed by four cycles of weekly paclitaxel). Primary endpoint was disease-free survival. At a median follow-up of 44.7 months, three-year disease-free survival rate was 92.3% in the carboplatin group and 85.8% in the control group (HR 0.64; p=0.03); this benefit was driven by reduction of recurrence in the first 12 months. Three-year overall survival rate was 98.0% in the carboplatin group and 94.0% in the control group (HR 0.41; p=0.01). The incidence of grade 3 or 4 treatment-related adverse events was 66.7% in the carboplatin group and 55.0% in the control group. No treatment-related deaths occurred. The authors conclude that the addition of carboplatin to adjuvant anthracycline-taxane based chemotherapy significantly improved survival outcomes in patients with high risk early stage TNBC.