Efficacy and safety of programmed cell death protein 1/programmed death-ligand 1 inhibitors combined with chemotherapy for breast cancer: a systematic review and meta-analysis

Background: Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), such as atezolizumab (Ate) and pembrolizumab (Pem), have expanded therapeutic options for breast cancer (BC). However, the comparative efficacy of ICI-chemotherapy (ICI-CT) combinations with different CT backbones [e.g., solvent-based paclitaxel vs. nab-paclitaxel (nP)] and the impact of steroid premedication (immunosuppressive, often required for solvent-based taxanes) on ICIs efficacy remain underexplored—gaps that hinder precise regimen selection. This meta-analysis evaluates the effectiveness of these regimens, focusing on triple-negative BC (TNBC) and PD-L1-positive populations. Methods: Searches were performed across PubMed, Embase, Cochrane and Web of Science to identify relevant studies comparing Ate- or Pem-based combinations (e.g., Ate + nP, Ate + CT, Pem + CT) with control regimens. Outcomes included overall survival (OS), progression-free survival (PFS), and subgroup analyses for TNBC. Meta-analyses were performed using random-effects models for pooled hazard ratios (HR) with corresponding 95% confidence intervals (CI). Heterogeneity was assessed using I2 statistics, and publication bias was evaluated using Cochran’s Q. Results: A total of 12 studies involving 6,691 patients were included in the analysis. Ate combined with nP significantly improved OS (HR =0.75; 95% CI: 0.65–0.86) and PFS (HR =0.69; 95% CI: 0.62–0.78) compared to placebo + CT. Pem + CT also enhanced OS (HR =0.70; 95% CI: 0.57–0.86; I2=4.9%) and PFS (HR =0.75; 95% CI: 0.65–0.87; I2=44.6%). In TNBC, Ate-based regimens showed superior OS (HR =0.90; 95% CI: 0.78–1.04; I2=24.2%) and PFS (HR =0.83; 95% CI: 0.75–0.91; I2=49.0%), while Pem demonstrated stronger OS benefits (HR =0.70; 95% CI: 0.57–0.86). Subgroup analysis revealed Ate + nP outperformed Ate + CT in OS (HR =0.75 vs. 1.18) and PFS (HR =0.69 vs. 0.81), though CT combinations required further validation due to limited data. Heterogeneity was relatively low for OS (I2=49.2%) and PFS (I2=65.4%). Conclusions: This is a relatively low-heterogeneity meta-analysis directly comparing Ate- and Pem-based combinations in BC. Ate + nP is the most effective regimen for PD-L1-positive TNBC, significantly improving survival. These findings support prioritizing Ate + nP for this population in clinical practice and underscore the need for biomarker-driven strategies to optimize immunotherapy efficacy. Future research should explore PD-L1 expression thresholds and CT sequencing to refine personalized treatment.