Neoadjuvant PD-1/PD-L1 inhibitors combined with chemotherapy in early-stage triple-negative breast cancer: A systematic review and meta-analysis.

Abstract

e12639 Background: Neoadjuvant immune checkpoint inhibition targeting the PD-1/PD-L1 pathway has become an integral component of treatment for early-stage triple-negative breast cancer (TNBC). While improvements in pathological complete response (pCR) have been consistently reported, the durability of benefit and the relevance of emerging survival data warrant integrated evaluation. We conducted a systematic review and meta-analysis to synthesize contemporary evidence, incorporating recent efficacy and survival updates. Methods: PubMed/MEDLINE and Cochrane CENTRAL were systematically searched to identify randomized and non-randomized studies evaluating neoadjuvant PD-1/PD-L1 inhibitors combined with chemotherapy in early-stage TNBC. Both published manuscripts and major conference presentations were reviewed to capture the most recent trial updates. Randomized controlled trials comparing chemo-immunotherapy with chemotherapy alone were eligible for quantitative synthesis of pCR, while event-free survival (EFS), overall survival (OS), and safety outcomes were summarized qualitatively using updated data. Study selection and synthesis followed PRISMA guidance. Results: Across randomized trials, neoadjuvant PD-1/PD-L1 inhibitors combined with chemotherapy consistently increased pCR rates compared with chemotherapy alone. Meta-analytic synthesis demonstrated a consistent and clinically meaningful increase in the likelihood of achieving pCR with the addition of immunotherapy. Updated analyses from landmark trials showed durable improvements in EFS, with emerging signals of OS benefit in high-risk early-stage TNBC. Real-world observational studies qualitatively corroborated trial findings, supporting the effectiveness of chemo-immunotherapy beyond controlled trial settings. Immune-related adverse events were more frequent with immunotherapy-containing regimens but were generally manageable and consistent with established safety profiles. Conclusions: Neoadjuvant PD-1/PD-L1 inhibitors combined with chemotherapy improve pathological response and are associated with durable survival signals in early-stage TNBC. This updated synthesis integrating contemporary trial updates reinforces neoadjuvant chemo-immunotherapy as a key component of modern treatment strategies and underscores the importance of continued follow-up to define long-term outcomes.