Toxicity profile and Tolerability of Immune Checkpoint Inhibitors for the Treatment of Early-Stage Breast Cancer: a Systematic Review and Meta-Analysis

Background Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis have demonstrated clinical benefit in early-stage breast cancer (eBC), enhancing antitumor immune responses. However, their incorporation into perioperative polychemotherapy has introduced new concerns regarding safety and immune-related toxicities (irAEs). We conducted a systematic review and meta-analysis to comprehensively evaluate the safety profile and tolerability of ICIs in patients with eBC. Methods A systematic review was conducted in PubMed, Embase, Cochrane Library, and relevant conference databases (ASCO, ESMO) to identify clinical trials reporting safety outcomes of ICIs in eBC. Data were analyzed using R (v4.2.2), applying random-effects models for both single-arm and comparative (pairwise) analyses. Results Thirteen studies were included, comprising 3,977 patients across all studies, including 3,138 treated with ICI-containing regimens and 839 controls. For comparative pairwise analyses, 2,715 patients received ICI-based therapy and 2,399 received chemotherapy alone. The most frequently reported all-grade AEs in ICI arms were alopecia (AR 86.49%, 95% CI: 59.25–96.57) and leukopenia (AR 52.09%, 95% CI: 15.14–86.89). For grade ≥3 events, decreased neutrophil count (AR 17.88%, 95% CI: 10.65–28.44) and neutropenia (AR 18.19%, 95% CI: 10.81–28.96) were most common. The most common irAE was hypothyroidism (AR 12.70%, 95% CI: 9.27—17.16), while the most frequent severe irAE (grade ≥3) was adrenal insufficiency (AR 1.47%, 95% CI: 0.68–3.12). Conclusion This meta-analysis provides a comprehensive evaluation of ICI safety in eBC. While most AEs were low-grade and manageable, significant risks of endocrine irAEs—particularly adrenal insufficiency and thyroid dysfunction—were identified. These findings underscore the need for proactive monitoring and highlight the importance of future research to better understand the mechanisms of ICI-related toxicity and to develop strategies for its prevention.