A network meta-analysis of endocrine adverse events induced by immune checkpoint inhibitors in colorectal cancer.

UNLABELLED: Immune checkpoint inhibitor (ICI) therapy for colorectal cancer (CRC) can be accompanied by endocrine adverse events, yet the comparative risk across commonly used regimens remains unclear. We therefore conducted a network meta-analysis of randomized controlled trials in CRC published up to November 22, 2025, estimating risk ratios (RRs) with 95% confidence intervals (CIs) and assessing risk of bias. Six RCTs were included. Relative to conventional therapy, ICI-based regimens were associated with a higher thyroid-related toxicity burden. Pembrolizumab and ICI+tyrosine kinase inhibitor (TKI) significantly increased the risk of hypothyroidism, whereas hyperthyroidism was significantly higher with ICI+TKI and ICI plus chemotherapy plus an anti-angiogenic antibody (ICI+Chem+Antiangio-Ab). Grade 1-2 adverse events were consistently increased across ICI-based treatments. For thyroiditis, diabetes mellitus, adrenal insufficiency, and grade 3-4 adverse events, effect estimates were imprecise with wide 95% CIs; nevertheless, SUCRA rankings tended to place ICI+TKI toward the higher-risk end for thyroiditis and diabetes. These findings indicate that ICI-containing strategies in CRC increase risks of endocrine adverse events-particularly for thyroid dysfunction-supporting the need for proactive endocrine monitoring and standardized management, while highlighting the limited precision of current evidence for rarer endpoints and severe toxicity.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD42023469312, identifier CRD42023469312.