Efficacy, survival, and safety of neoadjuvant immune checkpoint inhibitors plus chemotherapy in early breast cancer: A systematic review and meta-analysis of randomized and real-world comparative studies.

e12679 Background: Neoadjuvant chemotherapy is a standard approach for high-risk early breast cancer, with pathologic complete response serving as a validated surrogate for long-term outcomes in biologically aggressive subtypes. The addition of immune checkpoint inhibitors (ICIs) to neoadjuvant regimens has led to substantial improvement in pCR in multiple randomized trials. However, uncertainty remains regarding the consistency of benefit across subtypes, the magnitude of long-term survival gains, and the real-world generalizability of these findings. Methods: We performed a systematic review and meta-analysis of randomized controlled trials comparing neoadjuvant ICIs plus chemotherapy with chemotherapy alone in early-stage breast cancer. Pathologic complete response was pooled using odds ratios, time-to-event outcomes using hazard ratios with generic inverse variance methods, and safety outcomes using risk ratios. A real-world comparative cohort (Connors 2024) was included to enhance external validity. A total of 9 randomized controlled trials and 1 real-world comparative cohort were included. Results: Across 10 comparative studies including 5,354 patients (5,114 from RCTs and 240 from real-world comparative data), neoadjuvant ICI-based therapy demonstrated consistent and clinically meaningful benefits: Pathologic complete response:ICI-based therapy significantly increased the likelihood of achieving pCR (OR 1.55; 95% CI, 1.37–1.75; P < 0.00001; I² = 61%), with consistent benefit observed across major breast cancer subtypes. Event-free survival:Treatment with ICIs was associated with a significant reduction in disease-related events (HR 0.71; 95% CI, 0.58–0.87; P = 0.0008; I² = 32%), indicating improved durability of disease control. Overall survival:A statistically significant overall survival benefit was observed (HR 0.61; 95% CI, 0.48–0.78; P < 0.0001; I² = 27%), demonstrating that early gains in tumor response translated into long-term survival advantage. Grade ≥3 immune-related adverse events:ICI-based regimens were associated with a substantially higher risk of severe immune-related toxicity (RR 3.15; 95% CI, 2.25–4.40; P < 0.00001; I² = 85%), reflecting the need for vigilant toxicity monitoring and risk mitigation. Conclusions: In early-stage breast cancer, neoadjuvant immune checkpoint inhibitor–based therapy is associated with robust improvements in pathologic complete response and meaningful gains in event-free and overall survival, supported by both randomized and real-world comparative evidence. These benefits are accompanied by a substantially increased risk of severe immune-related adverse events, underscoring the importance of individualized risk–benefit assessment and optimization of patient selection and management strategies