A large-scale phase 3 clinical trial has found that adding carboplatin to standard adjuvant chemotherapy does not provide statistically significant survival benefits for patients with triple-negative breast cancer (TNBC), according to results presented at the 2025 American Society of Clinical Oncology Annual Meeting in Chicago.
The NRG-BR003 trial (NCT02488967) enrolled 769 patients with operable node-positive or high-risk node-negative TNBC between June 2015 and May 2022. Patients were randomly assigned to receive either standard dose-dense adjuvant chemotherapy consisting of doxorubicin/cyclophosphamide followed by weekly paclitaxel (control arm, n=385) or the same regimen with the addition of carboplatin administered intravenously every 3 weeks for 4 cycles (carboplatin arm, n=384).
Trial Design and Patient Population
The study was designed to detect a hazard ratio of approximately 0.67 in invasive disease-free survival (IDFS) with carboplatin addition. Most enrolled patients were over 50 years of age (66%), had primary tumors larger than 2 cm (70%), were node-positive (69%), and 9% had germline BRCA pathogenic variants. Stratification factors included the number of positive nodes and BRCA mutation status.
The primary endpoint was IDFS, with secondary endpoints including distant recurrence/relapse-free interval, overall survival, and adverse event frequencies. At the data cutoff on February 28, 2025, the median follow-up was approximately 79.4 months.
Key Efficacy Results
IDFS events occurred in 23.9% (92 patients) of the control group compared to 19.8% (76 patients) in the carboplatin group. However, the stratified log-rank test yielded a P value of 0.097, which did not meet the prespecified significance threshold of 0.049. The hazard ratio was 0.77 (95% CI, 0.57-1.05).
The 5-year IDFS rate was 77.8% (95% CI 73.7%-82.2%) in the control group versus 82.9% (95% CI 79.2%-86.9%) in the carboplatin group. Similar hazard ratios were observed across patient subgroups, including those with germline BRCA mutations and different nodal statuses.
Safety Profile and Adverse Events
The addition of carboplatin significantly increased toxicity rates. Treatment-related adverse events occurred in 51.1% of control patients compared to 72.9% of carboplatin patients. Grade 3 or higher adverse event rates were notably higher in the carboplatin arm, though grade 5 events remained low at 0.8% in both groups.
Despite the increased toxicity, paclitaxel delivery was not compromised by carboplatin co-administration, with patients receiving a mean of 11.3 doses and maintaining relative total dose intensity of approximately 0.95-0.97 across both arms.
Clinical Implications
The results indicate that carboplatin addition to standard adjuvant chemotherapy for TNBC does not meet efficacy criteria across the entire study population. The investigators noted that while there was a numerical improvement in survival outcomes, the lack of statistical significance, combined with increased toxicity, suggests limited clinical benefit for most patients.
The findings are particularly relevant given TNBC's aggressive nature and limited targeted treatment options due to the absence of hormone receptor expression. The study's negative results may influence treatment guidelines and clinical decision-making for this challenging breast cancer subtype.
Future Directions
Researchers emphasized that planned translational research may help identify specific subpopulations of TNBC patients who could potentially benefit from carboplatin addition to their treatment regimens. This precision medicine approach could help optimize therapy selection and improve outcomes for select patient groups while avoiding unnecessary toxicity in those unlikely to benefit.
