Evaluating the efficacy and safety of first-line immunotherapy for metastatic triple-negative breast cancer: a systematic review and network meta-analysis of randomized controlled trials with a focus on PD-L1 expression.

Introduction: This study systematically reviewed randomized controlled trials (RCTs) and conducted a Bayesian network meta-analysis to evaluate first-line immunotherapy regimens for metastatic triple-negative breast cancer (mTNBC), aiming to compare the efficacy and safety of different immunotherapy combinations and to explore the impact of programmed cell death ligand 1 (PD-L1) expression levels on survival benefits in patients. Methods: A comprehensive literature search was conducted across PubMed, Embase, Cochrane Library, and Web of Science databases. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and the incidence of grade ≥3 adverse events (AE≥3). A Bayesian network meta-analysis was conducted to evaluate the efficacy and safety of different immunotherapy regimens in the overall population and various PD-L1 expression subgroups (≥1%, ≥10%, and <1%). This study has been registered on PROSPERO (ID: CRD420251138714). Results: A total of 8 RCTs involving 3,789 patients and 6 immunotherapy combination regimens were included. Compared with chemotherapy alone, the combination of immune checkpoint inhibitors (ICIs) with chemotherapy significantly improved OS (HR = 0.90, 95% CI: 0.82-0.98) and PFS (HR = 0.82, 95% CI: 0.75-0.89) in the overall mTNBC population. The AE≥3 was slightly higher (OR = 1.20, 95% CI: 0.94-1.53) without statistical significance. In patients with PD-L1 expression ≥1%, ICIs combined with chemotherapy significantly improved OS (HR = 0.83, 95% CI: 0.74-0.93) and PFS (HR = 0.74, 95% CI: 0.66-0.82). In patients with PD-L1 ≥10%, the benefits for OS (HR = 0.68, 95% CI: 0.53-0.87) and PFS (HR = 0.68, 95% CI: 0.52-0.91) were even more pronounced. Toripalimab combined with chemotherapy (Toripa-chemo) showed the greatest OS benefit in the overall population (HR = 0.58, 95% CI: 0.38-0.87). Atezolizumab combined with Entinostat and chemotherapy (Atezo-Entino-chemo) showed a trend toward improved OS (HR = 0.49, 95% CI: 0.22-1.12) and ORR (OR = 5.14, 95% CI: 0.70-37.94). Pembrolizumab combined with chemotherapy (Pembro-chemo) demonstrated the best safety profile (OR = 1.06, 95% CI: 0.52-2.16). Subgroup analysis showed that in patients with PD-L1 ≥ 1%, Toripa-chemo conferred the greatest benefit, with the most favorable OS (HR = 0.67, 95% CI: 0.40-1.12) and PFS (HR = 0.64, 95% CI: 0.47-0.87). Conversely, in patients with PD-L1 <1%, Pembro-chemo showed the best OS benefit (HR = 0.97, 95% CI: 0.72-1.31). Conclusions: Compared to chemotherapy alone, immunotherapy combined with chemotherapy significantly improves survival outcomes in mTNBC patients, with more pronounced benefits observed in the PD-L1 positive population. Toripa-chemo and Pembro-chemo demonstrate a balanced profile of efficacy and safety, suggesting that they may be suitable options for first-line treatment of mTNBC. Among these, Toripa-chemo may be considered a preferred first-line regimen for PD-L1 positive patients. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier ID: CRD420251138714.