Multicenter phase 3 trial of a multigene signature for tailoring adjuvant chemotherapy for triple-negative breast cancer

Previous studies showed that an integrated signature of three mRNAs and two lncRNAs could effectively classify TNBC patients into groups at high risk or low risk for disease recurrence. A phase 3 trial at 7 centers in China evaluated the feasibility of using this signature to tailor adjuvant chemotherapy for TNBC. Patients with high-risk disease according to the signature were randomized to intensive chemotherapy (arm A) or standard chemotherapy (arm B). Patients with low-risk disease according to the signature (arm C) received the same chemotherapy as patients in arm B. Three-year disease-free survival rate was 90.9% in arm A versus 80.6% in arm B (HR 0.51; p=0.03); three-year recurrence-free survival rate was 92.6% versus 80.6% (HR 0.50; p=0.04); and three-year overall survival rate was 98.2% versus 91.3% (HR 0.58; p=0.27). The outcomes in arm C were significantly better than in arm B with the same chemotherapy regimen. The incidence of grade 3 or 4 treatment-related adverse events was 64% in arm A, 51% in arm B, and 54% in arm C. There were no grade 5 TRAEs. The authors conclude that the multigene signature showed potential for tailoring adjuvant chemotherapy for TNBC. Among high-risk patients, intensive chemotherapy significantly improved DFS with manageable toxicity.