New research finds that adding carboplatin to paclitaxel and adjuvant chemotherapy shows no significant survival benefits in triple-negative breast cancer (TNBC).
Study findings demonstrated that the addition of carboplatin (Paraplatin; Bristol-Myers Squibb) to paclitaxel (Taxol; Pfizer) following dose-dense doxorubicin (Adriamycin; Pfizer)/cyclophosphamide (Cytoxan; Baxter Healthcare) for adjuvant therapy of node-positive or high-risk node-negative triple-negative breast cancer (TNBC) did not result in statistically significant improvements in invasive disease-free survival (IDFS), distant recurrence/relapse-free interval (DRFI), or overall survival (OS). These data were presented as part of the 2025 American Society of Clinical Oncology Annual Meeting (ASCO), which was held in Chicago, Illinois.1
These data are from the NRG-BR003 trial (NCT02488967)2, a randomized phase 3 trial assessing whether the addition of carboplatin to an adjuvant chemotherapy regimen (doxorubicin/cyclophosphamide) followed by paclitaxel will improve IDFS in patients with operable node-positive or high-risk node-negative TNBC. Patients eligible for treatment were randomly assigned to receive dose-dense adjuvant chemotherapy every 2 weeks for 4 cycles followed by weekly paclitaxel (80 mg/m2) for 12 doses or the same regimen with carboplatin intravenously every 3 weeks for 4 cycles. Stratification factors were the number of positive nodes (0, 1-3, 4-9, 10+) and BRCA mutation status (positive, negative, or unknown).1,2
The primary end point was IDFS, with secondary end points being DRFI, OS, biochemical recurrence-free survival rate, RFI, as well as frequencies of adverse events (AEs). Further, the investigators noted that the study was designed to detect an HR in IDFS at about 0.67 with the addition of carboplatin. The stratified log-rank test was used for the primary analysis.1,2
Trial Name: Doxorubicin Hydrochloride and Cyclophosphamide Followed by Paclitaxel With or Without Carboplatin in Treating Patients With Triple-Negative Breast Cancer
ClinicalTrials.gov ID: NCT02488967
Sponsor: NRG Oncology
Completion Date (Estimated): October 31, 2026
A total of 769 patients were enrolled and randomly assigned to the control arm (n = 385) and the carboplatin arm (n = 384) from June 2015 to May 2022. Most patients were over the age of 50 years (66%), had primary tumors larger than 2 cm (70%), were node-positive (69%), and some had germline BRCA (gBRCA) pathogenic variants (9%). Of note, the delivery of adjuvant chemotherapy was balanced between arms, and paclitaxel delivery was not compromised by coadministration of carboplatin (mean: 11.3 doses). Paclitaxel had a relative total dose intensity (RTDI) of about 0.97 and 11.0 doses in the control arm and an RTDI of 0.95 in the carbo arm. On February 28, 2025, which was the time of data cutoff, the median follow-up was about 79.4 months.1
The findings demonstrated that IDFS events were reported in about 23.9% (n = 92) of patients in the control group and 19.8% (n = 76) in the carboplatin group. In addition, the stratified log-rank test P value was about .097, which did not meet the prespecified significance of .049. The HR was about 0.77 (95% CI, 0.57-1.05).1
Further, the 5-year IDFS was approximately 77.8% (95% CI, 73.7%-82.2%) in the control group compared with 82.9% (95% CI, 79.2%-86.9%) in the carboplatin group. HR was observed to be similar across patient subgroups, including gBRCA and nodal status. Treatment-related AE rates were approximately 51.1% in the control group and 72.9% in the carboplatin group, but grade 5 events were 0.8% in both groups.1
Not only did the addition of carboplatin to paclitaxel in adjuvant chemotherapy not appear to result in statistically significant improvements, but grades 3 and higher AE rates increased. As a result, the investigators noted that these data did not meet criteria for efficacy across the entire study population and suggested that planned translational research may identify the subpopulations of patients who may benefit from carboplatin added to their treatment regimens.1
