A network meta-analysis of endocrine adverse events induced by immune checkpoint inhibitors in colorectal cancer
In brief
Pembrolizumab and ICI-TKI combos raise hypothyroidism risk in colorectal cancer
In a network meta-analysis of six colorectal-cancer trials, immune checkpoint inhibitor regimens showed a higher burden of thyroid-related toxicity than conventional therapy, with pembrolizumab and ICI-TKI combinations significantly increasing hypothyroidism and ICI-TKI or ICI-chemo-anti-angiogenic regimens raising hyperthyroidism. Grade 1-2 endocrine events were consistently more common, while estimates for thyroiditis, diabetes, adrenal insufficiency, and severe toxicity remained imprecise, underscoring the need for proactive endocrine monitoring.
- Journal
- Frontiers in immunology (Q1)
- Published
- 10 July 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Boyu Chen, Jing Liu, Kexin Gan, Liqun Yang, Peng Qiu, Boqing Ma, et al.
- PMID
- 42500681
- DOI
- 10.3389/fimmu.2026.1798732
Why clinicians should know about it
- Picked for Endocrinology, Diabetes and Metabolism (paper of the day, 26 July 2026).
- Picked for Gastroenterology (paper of the day, 26 July 2026): Recent Gastroenterology research from a high-quartile journal
- Picked for Public Health, Environmental and Occupational Health (top studies of the week, 26 July 2026).
- Picked for Oncology and Radiation Oncology (top studies of the week, 26 July 2026): Network meta‑analysis of endocrine AEs from ICIs in colorectal cancer
- Picked for Immunology and Allergy (top studies of the week, 26 July 2026).
Abstract
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.
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.