Endocrine Abstracts

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.