Cited by 381Cancer Immunotherapy and BiomarkersAdrenal Hormones and DisordersPituitary Gland Disorders and Treatments

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A Systematic Review and Meta-Analysis of Endocrine-Related Adverse Events Associated with Immune Checkpoint Inhibitors

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de Filette, Jeroen, Andreescu, Corina, Cools, Filip, Bravenboer, Bert, Velkeniers, Brigitte·2019·Hormone and Metabolic Research

DOI 10.1055/a-0843-3366

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Abstract

Monoclonal antibodies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4), programed cell death 1 (PD-1), or its ligand (PD-L1) have become the mainstay for advanced malignancies. The incidence of endocrine adverse events provoked by these immune checkpoint inhibitors (ICI) is based on data from randomized controlled trials, which have their drawbacks. PubMed was searched through August 22nd, 2017, by 2 reviewers independently (J.d.F. and C.E.A.). Early phase I/II, phase III experimental trials, prospective and retrospective observational studies were included. The weighted incidence and risk ratio were estimated for hypophysitis, primary thyroid disease, primary adrenal insufficiency, and diabetes mellitus. Their management is discussed in a systematic review. A total of 101 studies involving 19 922 patients were included. Ipilimumab-treated patients experienced hypophysitis in 5.6% (95% CI, 3.9–8.1), which was higher than nivolumab (0.5%; 95% CI, 0.2–1.2) and pembrolizumab (1.1%; 95% CI, 0.5–2.6). PD-1/PD-L1 inhibitors had a higher incidence of thyroid dysfunction – particularly hypothyroidism (nivolumab, 8.0%; 95% CI, 6.4–9.8; pembrolizumab, 8.5%; 95% CI, 7.5–9.7; PD-L1, 5.5%; 95% CI, 4.4–6.8; ipilimumab, 3.8%; 95% CI, 2.6–5.5). Combination therapy was associated with a high incidence of hypothyroidism (10.2–16.4%), hyperthyroidism (9.4–10.4%), hypophysitis (8.8–10.5%), and primary adrenal insufficiency (5.2–7.6%). Diabetes mellitus and primary adrenal insufficiency were less frequent findings on monotherapy. Our meta-analysis shows a high incidence of endocrine adverse events provoked by single agent checkpoint blockade, further reinforced by combined treatment.

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Authors: de Filette, J., Andreescu, C., Cools, F., Bravenboer, B., & Velkeniers, B.
Affiliations: Department of Endocrinology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium
Vrije Universiteit Brussel (BE)
ORCID: Andreescu, Corina
Cools, Filip
Bravenboer, Bert
Velkeniers, Brigitte
Venue: Hormone and Metabolic Research
Publisher: Georg Thieme Verlag KG
Published: 2019-03
Volume: 51
Issue: 03
Pages: 145-156
ISSN: 0018-5043 (ISSN-L)
1439-4286
DOI: 10.1055/a-0843-3366
OpenAlex: W2921353943
Cited by: 381
References: 156
Citations by year: 2026: 45 · 2025: 57 · 2024: 43 · 2023: 64 · 2022: 64 · 2021: 48 · 2020: 46 · 2019: 14
FWCI: 4.10
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Hormone and Metabolic Research (publishedVersion)
PubMed (publishedVersion)
VUBIR (Vrije Universiteit Brussel) (submittedVersion)
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
Keywords: immune checkpoint inhibitors, endocrine adverse events, hypophysitis, Addison's disease, thyroid dysfunction, hypothyroidism, hyperthyroidism, diabetes mellitus, CTLA-4 blockade, PD-1/PD-L1 blockade, ipilimumab, nivolumab, pembrolizumab, combination immunotherapy
MeSH terms: Hypophysitis, Antineoplastic Agents, Immunological, Addison Disease, Diabetes Mellitus, Humans, Neoplasms, Thyroid Diseases

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A Systematic Review and Meta-Analysis of Endocrine-Related Adverse Events Associated with Immune Checkpoint Inhibitors

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