Efficacy, safety, and PD-L1-defined outcomes of neoadjuvant immune checkpoint inhibitors in early-stage triple-negative breast cancer: a systematic review and meta-analysis
In brief
Neoadjuvant immunotherapy raises complete response rate by 27% in early triple-negative breast cancer
Adding immune checkpoint inhibitors to chemotherapy increased pathological complete response by about one-quarter compared with chemotherapy alone in four phase III trials of 3,377 patients, and the benefit was seen regardless of PD-L1 status. Severe overall toxicity was unchanged, but immune-related side effects more than tripled, highlighting a trade-off and the need for better selection tools.
- Journal
- Frontiers in immunology (Q1)
- Published
- 12 August 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Chang Ma, Hoon Koon Teoh, Delai Qiu, Yingnan Zhang, Shubao Yang, Yang Zhao, et al.
- PMID
- 42656671
- DOI
- 10.3389/fimmu.2026.1933897
Why clinicians should know about it
- Picked for Oncology and Radiation Oncology (top studies of the week, 30 August 2026): Meta‑analysis of neoadjuvant ICI + chemo in early TNBC
- Picked for Pathology and Forensic Medicine (top studies of the week, 30 August 2026): High-quality evidence in a top journal
- Picked for Pharmacology (medical) (top studies of the week, 30 August 2026): Neoadjuvant ICI meta‑analysis in TNBC
Abstract
BACKGROUND: Neoadjuvant immune checkpoint inhibitors combined with chemotherapy improve pathological complete response in early-stage triple-negative breast cancer, but the consistency of benefit, role of PD-L1 expression, and immune-related toxicity remain clinically relevant. METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception to June 30, 2026, for randomized trials comparing neoadjuvant immune checkpoint inhibitors plus chemotherapy with chemotherapy alone or placebo plus chemotherapy in early-stage triple-negative breast cancer. The primary efficacy analysis was restricted to phase III trials. Risk ratios and 95% confidence intervals were pooled using a random-effects model. Risk of bias and certainty of evidence were assessed using RoB 2 and GRADE. RESULTS: Four phase III trials including 3,377 patients were included in the primary efficacy synthesis. Neoadjuvant immune checkpoint inhibitors plus chemotherapy significantly increased pathological complete response compared with control treatment (risk ratio, 1.27; 95% confidence interval, 1.19-1.36; P < 0.001), with no statistical heterogeneity. Benefit was observed in both PD-L1-positive tumors (risk ratio, 1.32; 95% confidence interval, 1.18-1.48) and PD-L1-negative tumors (risk ratio, 1.45; 95% confidence interval, 1.22-1.72). Grade ≥ 3 treatment-related adverse events were not significantly increased (risk ratio, 1.06; 95% confidence interval, 0.98-1.13), whereas immune-related adverse events were more frequent with immune checkpoint inhibitors (risk ratio, 3.52; 95% confidence interval, 1.88-6.57). CONCLUSIONS: Neoadjuvant immune checkpoint inhibitors plus chemotherapy improve pathological complete response in early-stage triple-negative breast cancer, including across PD-L1-defined subgroups, but increase immune-related toxicity. PD-L1 expression alone appears insufficient for treatment selection. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/recorddashboard#, identifier CRD420261412366.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.