The following is a summary of “Risk and Incidence of Endocrine Immune-Related Adverse Effects Under Checkpoint Inhibitor Mono- or Combination Therapy in Solid Tumors: A Meta-Analysis of Randomized Controlled Trials,” published in the April 2024 issue of Endocrinology by Vardarli, et al.
Despite the publication of a few meta-analyses on the incidence of endocrine immune-related adverse effects (eirAEs), many trials have been conducted since then, necessitating an updated and comprehensive literature analysis. For a study, researchers sought to perform a comprehensive meta-analysis, incorporating updated literature, to evaluate the risk and incidence of eirAEs, both of any grade and grade 3 to 5, associated with immune checkpoint inhibitor (ICI) monotherapy or combination therapy in solid tumors.
A systematic electronic search was conducted using PubMed/Medline, Embase, and the Cochrane Library. Randomized controlled trials (RCTs) assessing eirAEs under ICI monotherapy or combination therapy were included. Statistical analyses were performed using Stata software (v17), and the risk of bias was evaluated using Review Manager version 5.3.
In total, 69 RCTs were included, with 80 independent reports involving 42,886 patients. The meta-analysis revealed pooled estimates for risk ratio and incidence for various eirAEs, including hypothyroidism (7.81 [95% CI, 5.68-10.74, P < .0001] and 7.64% [95% CI, 6.23-9.17, P < .0001], respectively), hyperthyroidism, hypophysitis/hypopituitarism, adrenal insufficiency, and insulin-dependent diabetes mellitus (1.52 [95% CI, 1.07-2.18, P = .02] and 0.087% [95% CI, 0.019-0.189, P = .0006], respectively). Notably, the risk and incidence of eirAEs were substantially increased with ICI therapy, independent of cancer type. Furthermore, the combination of ICIs, specifically nivolumab plus ipilimumab and durvalumab plus tremelimumab, was identified as an independent risk factor for certain eirAEs, particularly hypophysitis/hypopituitarism.
This meta-analysis underscored the heightened risk and incidence of eirAEs associated with ICI therapy, regardless of cancer type. Importantly, combination ICIs were found to significantly increase the risk of eirAEs, particularly hypophysitis/hypopituitarism. The findings emphasized the need for vigilant monitoring and management of eirAEs in patients receiving ICI therapy.
Reference: academic.oup.com/jcem/article-abstract/109/4/1132/7423989