Platinum-based chemotherapy in early-stage, high-risk, triple-negative breast cancer: A systematic review and meta-analysis of randomized trials.

Abstract

529 Background: The clinical benefit of adding platinum agents to adjuvant chemotherapy for early-stage triple-negative breast cancer (TNBC) remains uncertain. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the impact of carboplatin-based adjuvant chemotherapy on survival outcomes in patients with early-stage, high-risk TNBC. Methods: RCTs comparing carboplatin plus standard adjuvant chemotherapy versus chemotherapy alone in early-stage, high-risk TNBC were identified through systematic searches of PubMed, Embase, Cochrane CENTRAL, and major oncology meeting proceedings. The primary endpoint was disease-free survival (DFS). Secondary endpoints included recurrence-free survival (RFS), distant disease–free survival (DDFS), and overall survival (OS). Hazard ratios (HRs) were pooled using random-effects models. Absolute survival differences at fixed timepoints were estimated using reconstructed individual patient–level data derived from published Kaplan–Meier curves. Results: Five randomized trials enrolling 3,153 patients were included; 1,576 (49.9%) received carboplatin-based chemotherapy. Median age ranged from 47 to 56 years, and most patients had grade 3 tumors and node-positive disease. Carboplatin-based chemotherapy significantly improved DFS compared with chemotherapy alone (HR 0.66, 95% CI 0.62–0.71; p < 0.001). Consistent proportional benefits were observed for RFS (HR 0.66, 95% CI 0.62–0.71; p < 0.001), DDFS (HR 0.66, 95% CI 0.62–0.71; p < 0.001) and OS (HR 0.66, 95% CI 0.62–0.71; p < 0.001), with no substantial between-trial heterogeneity (I² < 25% for all endpoints). Reconstructed survival analyses demonstrated increasing absolute benefit over time. At 3 years, carboplatin-based chemotherapy was associated with absolute improvements of approximately 4–6% in DFS and 3–5% in OS. At 5 years, absolute differences favored carboplatin by approximately 7–9% for DFS, 6–9% for RFS, 6–8% for DDFS, and 6–8% for OS (log-rank p < 0.001 for all comparisons). DFS benefit was observed across clinically relevant subgroups, including node-negative (HR 0.69, 95% CI 0.53–0.90) and node-positive disease (HR 0.57, 95% CI 0.37–0.86), as well as among patients with and without germline BRCA1/2 mutations. Greater proportional benefit was observed in patients with grade III tumors and pT2–T3 disease. Conclusions: Across RCTs, the addition of carboplatin to standard adjuvant chemotherapy was associated with significant and durable improvements in DFS and OS in patients with early-stage, high-risk TNBC. Absolute survival gains increased with longer follow-up, supporting the clinical relevance of platinum-based adjuvant strategies in selected high-risk populations.