J Clin Endocrinol Metab. 2023 Nov 15:dgad670. doi: 10.1210/clinem/dgad670. Online ahead of print.
ABSTRACT
CONTEXT: Few meta-analyses regarding the incidence of endocrine immune related adverse effects (eirAEs) have been published and many trials were published thereafter.
OBJECTIVE: To assess the risk and incidence of eirAEs of any grade and grade 3-5 by immune checkpoint inhibitor (ICI) mono or combination-therapy in solid tumors current literature was updated in this comprehensive meta-analysis.
METHODS: An electronic search using PubMed/Medline, Embase and the Cochrane Library was performed. Randomized controlled studies (RCT) assessing eirAEs under ICI-mono or ICI-combination therapy were selected. Stata software version 17 was used for statistical analyses and risk of bias was evaluated by using Review Manager version 5.3.
RESULTS: 69 RCTs with 80 independent reports, involving 42,886 patients were included in the study. Meta-analysis revealed the following pooled estimates for the risk ratio and the incidence, respectively: for any grade hypothyroidism 7.81 (95% CI, 5.68-10.74, p< 0.0001) and 7.64% (95% CI, 6.23-9.17, p< 0.0001); significantly increased also for hyperthyroidism, hypophysitis/hypopituitarism and adrenal insufficiency; and for insulin-dependent diabetes mellitus 1.52 (95% CI, 1.07-2.18, p= 0.02), and 0.087% (95% CI, 0.019-0.189, p= 0.0006), respectively. Meta-regression showed that combination of ICIs (nivolumab plus ipilimumab and durvalumab plus tremelimumab, respectively) is an independent risk factor for any grade hypophysitis/hypopituitarism, and that ICI agent is an independent factor of risk for adrenal insufficiency, but that cancer type is not an independent risk factor for eirAEs.
CONCLUSION: We showed that risk, independent from cancer type, and incidence of eAEs are substantially increased under ICI therapy. Combination of ICIs is increasing the risk for eirAEs, in particular for hypophysitis/hypopituitarism.
PMID:37967245 | DOI:10.1210/clinem/dgad670
