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A Systematic Review and Meta-Analysis of Endocrine-Related Adverse Events Associated with Immune Checkpoint

Jeroen de Filette1, Corina Emilia Andreescu1, Filip Cools2

  • 1Department of Endocrinology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium.

Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Metabolisme
|March 13, 2019
PubMed

Insights

Immune checkpoint inhibitors (ICIs) like CTLA-4, PD-1, and PD-L1 can cause endocrine issues. This meta-analysis reveals a high incidence of these adverse events, especially with combination therapies.

Area of Science:

  • Oncology
  • Immunology
  • Endocrinology

Background:

  • Immune checkpoint inhibitors (ICIs) targeting CTLA-4, PD-1, or PD-L1 are standard treatments for advanced cancers.
  • The incidence of endocrine adverse events from ICIs is not fully characterized, particularly from real-world data.
  • Randomized controlled trials have limitations in capturing the full spectrum of ICI-induced endocrine toxicities.

Purpose of the Study:

  • To systematically review and meta-analyze the incidence of endocrine adverse events associated with immune checkpoint inhibitors.
  • To compare the risk of endocrine toxicities among different ICI agents (ipilimumab, nivolumab, pembrolizumab) and combination therapies.
  • To provide a comprehensive overview of ICI-induced hypophysitis, thyroid dysfunction, adrenal insufficiency, and diabetes mellitus.

Main Methods:

  • A systematic literature search of PubMed was conducted up to August 22nd, 2017.
  • Included studies comprised early phase I/II, phase III trials, and observational studies (prospective and retrospective).
  • Weighted incidence and risk ratios for specific endocrine adverse events were estimated across 101 studies involving 19,922 patients.

Main Results:

  • Hypophysitis incidence was higher with ipilimumab (5.6%) compared to nivolumab (0.5%) and pembrolizumab (1.1%).
  • PD-1/PD-L1 inhibitors showed a higher incidence of hypothyroidism (8.0-8.5%) than ipilimumab (3.8%).
  • Combination ICI therapy significantly increased the incidence of hypothyroidism (10.2-16.4%), hyperthyroidism (9.4-10.4%), hypophysitis (8.8-10.5%), and adrenal insufficiency (5.2-7.6%).

Conclusions:

  • Single-agent checkpoint blockade therapy is associated with a substantial incidence of endocrine adverse events.
  • Combination ICI therapy further elevates the risk and incidence of these endocrine toxicities.
  • Awareness and monitoring for endocrine adverse events are crucial in patients receiving ICI therapy.

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