Efficacy and safety of immune checkpoint inhibitors plus chemotherapy in early-stage triple-negative breast cancer: a systematic review and meta-analysis
Abstract
Immune checkpoint inhibitors combined with chemotherapy have improved pathological responses in early-stage triple-negative breast cancer (TNBC), but the magnitude of benefit and associated toxicity remain variable across trials. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of immunotherapy plus chemotherapy in patients with early-stage or high-risk TNBC. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to March 2026 for randomized controlled trials (RCTs). The primary outcome was pathological complete response (pCR). Dichotomous outcomes were pooled as risk ratios (RRs) with 95% confidence intervals (CIs). Between-study heterogeneity was assessed using Cochran’s Q test and the I² statistic. Exploratory subgroup analyses were conducted according to programmed death-ligand 1 (PD-L1) expression and lymph node status. Five RCTs were included. Immunotherapy plus chemotherapy was associated with a higher pCR rate than control regimens (RR = 1.44, 95% CI 1.09–1.79), with substantial heterogeneity (I² = 83.7%). In exploratory analyses, the pooled RR was 1.36 (95% CI 1.18–1.57) in PD-L1-positive patients and 1.18 (95% CI 0.96–1.45) in PD-L1-negative patients. Corresponding RRs were 1.42 (95% CI 1.19–1.69) for node-positive and 1.21 (95% CI 1.02–1.43) for node-negative disease. Immunotherapy-containing regimens were also associated with higher risks of grade 3–4 adverse events (RR = 1.18, 95% CI 1.05–1.33), serious adverse events (RR = 1.42, 95% CI 1.12–1.79), and treatment discontinuation due to adverse events (RR = 1.67, 95% CI 1.18–2.36). Immunotherapy combined with chemotherapy was associated with higher pCR rates in early-stage or high-risk TNBC but also with greater treatment-related toxicity. PD-L1 and nodal subgroup findings should be considered exploratory, and further evidence is needed to clarify long-term clinical outcomes. [url], identifier [].