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Endocrine Abstracts (2018) 56 GP211 | DOI: 10.1530/endoabs.56.GP211

ECE2018 Guided Posters Pituitary Clinical (12 abstracts)

A systematic review and meta-analysis of endocrine-related adverse events associated with immune checkpoint inhibitors

Jeroen de Filette , Corina Andreescu , Filip Cools , Bert Bravenboer & Brigitte Velkeniers


University Hospital Brussels, Brussels, Belgium.


Background: Monoclonal antibodies targeting CTLA-4 and PD-1/PD-L1 are promising for a wide range of advanced malignacies. These immune checkpoint inhibitors (ICI) provoke endocrine adverse events including hypopituitarism and primary thyroid disease.

Methods: PubMed was searched through August 22nd, 2017, for relevant articles on endocrinopathies and ICI, by two reviewers independently (J.d.F. and C.A.). The weighted incidence and odds-ratio were estimated for hypophysitis, primary thyroid disease, primary adrenal insufficiency and diabetes mellitus. Their management is discussed in a systematic review.

Results: One hundred and one clinical studies (retrospective, prospective and randomized trials) involving 19.922 patients were included. Patients treated with ipilimumab experienced hypophysitis in 5.6% (95% CI, 3.9–8.1) which was higher than PD-1 treated patients (nivolumab, 0.5%; 95% CI, 0.2–1.2; pembrolizumab, 1.1%; 95% CI, 0.5–2.6). Tremelimumab (anti-CTLA-4) was also less likely to induce hypophysitis (1.8%; 95% CI, 1.1–2.9). Patients on PD-1/PD-L1 inhibitors had a higher incidence of primary thyroid dysfunction – particularly hypothyroidism (nivolumab, 8.0%; 95% CI, 6.4–9.8; pembrolizumab, 8.7%; 95% CI, 7.9–9.6; PD-L1, 5.5%; 95% CI, 4.4–6.8; versus ipilimumab, 3.8%; 95% CI, 2.6–5.5). Combination therapy was associated with a higher incidence for both hypothyroidism (10.2–16.4%) and hypophysitis (8.7–10.5%). Diabetes mellitus and primary adrenal insufficiency, rare findings on monotherapy, were substantially more frequent on combined therapy.

Conclusion: Our systematic review and meta-analysis demonstrates a high incidence of endocrine adverse events provoked by single agent checkpoint blockade which is further reinforced by combined treatment.

Volume 56

20th European Congress of Endocrinology

Barcelona, Spain
19 May 2018 - 22 May 2018

European Society of Endocrinology 

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