Endocrine Abstracts

Background: Immune checkpoint inhibitors (ICI) have become a clinically validated treatment for numerous types of tumor including melanoma, lung, and kidney carcinoma. These treatments can cause immune-related adverse events affecting several organs including the endocrine system.

Aims: The aim of this study was to characterize the type and the onset of the ICI associated-endocrinopathies.

Materials and methods: This retrospective cohort evaluation included patients with advanced cancer candidate for ICI treatment attending the Oncology Unit at S.Orsola-Malpighi Hospital of Bologna from January2016 to September2017. All patients were treated with a different schedule according to the Authority-approved ICI doses and administration.

Results: Sixty-nine patients were included in this study and they were followed for 32 weeks in average (range 2 to 88 weeks). Fifty-one patients were treated with nivolumab (n=23 lung-carcinoma, n=22 melanoma, n=6 kidney-carcinoma), 12 with pembrolizumab (n=10 melanoma, n=2 lung-carcinoma), 4 with ipilimumab (n=2 kidney carcinoma, n=2 melanoma), and 2 with ipilimumab+nivolumab (n=1 melanoma, n=1 liver-cancer). Among these 69 cases, 10 (14.5%) showed drug-induced endocrinopathies: 1 had a central hypoadrenalism with ipilimumab, 1 had a sudden-onset of diabetes mellitus with nivolumab, and 8 developed thyrotoxicosis with nivolumab (n=5), with ipilimumab+nivolumab (n=2) and with pembrolizumab (n=1). Central hypoadrenalism and diabetes developed at 4th (12 weeks) and at the 26th drug administration (52 weeks), respectively. These subjects required gluco-corticoid and insulin lifelong replacement therapy, respectively. Instead, thyrotoxicosis induced by nivolumab and pembrolizumab occurred at the 3rd drug administration (6-9 weeks), whereas those caused by ipilimumab+nivolumab appeared in one subject at the 3rd (6 weeks) and the other at the 7th drug administration (14 weeks). The average time of thyrotoxicosis was 3 weeks (1-8 weeks). Of these 8 thyrotoxicosis, 4 subjects progressed to overt hypothyroidism (n=2 nivolumab, n=2 ipilimumab+nivolumab) and 4 to euthyroidism (n=3 nivolumab, n=1 pembrolizumab). All these subjects had no previous history of thyroid disease. The etiology of the endocrinopathies are presumably immune, however the specific known autoimmunity in selected patients was negative (anti-GAD antibodies for diabetes, and anti-thyroid peroxidase, anti-tireoglobulin, anti-TSH receptors in 2 thyrotoxicosis).

Conclusion: In our clinical records, endocrine related adverse events were relatively common with thyrotoxicosis being the most frequent. All adverse events were successfully managed without needing to stop ICI treatment. These findings suggest that a close interaction between the endocrinologist and oncologist should be advocated for a rapid identification and treatment of ICI-induced endocrinopathies.