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

The DOI matches its Crossref record; 156 of the 156 references it cites were found in a registry or an index.

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

Open access
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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  1. Theodossiou C, Skrepnik N, Robert EG et al. Propylthiouracil-induced hypothyroidism reduces xenograft tumor growth in athymic nude mice. Cancer 1999; 86: 1596-1601
  2. Matsumura K, Nagasawa K, Oshima Y et al. Aggravation of diabetes, and incompletely deficient insulin secretion in a case with type 1 diabetes-resistant HLA DRB1 * 15:02 treated with nivolumab. J Diabetes Invest 2017; 9: 438-441

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Metadata

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
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
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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