A phase 3 trial conducted in China has demonstrated the potential of a multigene signature to personalize adjuvant chemotherapy for patients with operable triple-negative breast cancer (TNBC). The study found that high-risk patients, identified using the signature, experienced significantly improved disease-free survival (DFS) when treated with an intensive chemotherapy regimen incorporating gemcitabine and cisplatin, compared to standard anthracycline/taxane-based chemotherapy.
Tailoring Treatment with Multigene Signatures
The study, known as BCTOP-T-A01, enrolled 504 women aged 18-70 with early-stage TNBC across seven cancer centers in China. Researchers used an integrated mRNA-lncRNA signature to classify patients as either high-risk or low-risk for disease recurrence. High-risk patients were then randomized to receive either intensive adjuvant chemotherapy (docetaxel, epirubicin, and cyclophosphamide followed by gemcitabine and cisplatin) or standard chemotherapy (epirubicin and cyclophosphamide followed by docetaxel).
Improved Disease-Free Survival
After a median follow-up of 45.1 months, the three-year DFS rate was 90.9% in the intensive chemotherapy arm (Arm A) compared to 80.6% in the standard chemotherapy arm (Arm B), with a hazard ratio of 0.51 (95% CI: 0.28-0.95, P=0.03). The three-year recurrence-free survival (RFS) rate was also higher in Arm A (92.6%) than in Arm B (83.2%), with a hazard ratio of 0.50 (95% CI: 0.25-0.98, P=0.04).
Validation of Prognostic Value
The study also validated the prognostic value of the multigene signature. Low-risk patients (Arm C), who received the same standard chemotherapy regimen as Arm B, had significantly higher rates of DFS (90.1%), RFS (94.5%), and overall survival (OS) compared to high-risk patients receiving standard chemotherapy. The three-year overall survival rate was 100% in Arm C compared to 91.3% in Arm B (hazard ratio 0.14, 95% CI: 0.03 to 0.61; P=0.002).
Safety and Tolerability
While the intensive chemotherapy regimen was associated with a higher incidence of grade 3 or 4 treatment-related adverse events (64% in Arm A vs. 51% in Arm B), these were primarily hematological toxicities, such as neutropenia and thrombocytopenia, and were generally manageable with supportive care. No treatment-related deaths occurred in the study.
Implications for Clinical Practice
The findings suggest that the multigene signature can effectively identify TNBC patients who are most likely to benefit from more aggressive adjuvant chemotherapy. "This phase 3 trial marks a pivotal advance, showing for the first time the feasibility of using multigene signatures to tailor individualised adjuvant therapy for patients with operable triple negative breast cancer," the study authors noted.
Future Directions
While the study provides compelling evidence for personalized treatment strategies in TNBC, further research is needed to validate these findings in diverse ethnic populations and to explore the applicability of the multigene signature in various clinical settings, including neoadjuvant therapy and treatment de-escalation strategies for low-risk patients.
