Thyroid Dysfunction in Non-Small Cell Lung Cancer With Immune Checkpoint Inhibitors: A Meta-Analysis

J Clin Pharmacol. 2023 Feb;63(2):210-218. doi: 10.1002/jcph.2150. Epub 2022 Nov 2.

Abstract

Immune checkpoint inhibitors (ICIs) have been established as the cornerstone for advanced non-small cell lung cancer, while thyroid adverse events (AEs) associated with ICIs have not been systematically documented. Therefore, we performed a meta-analysis to evaluate the effect of ICI applications on the thyroid of patients with non-small cell lung cancer. We performed a systematic search of PubMed, the Cochrane Library, Web of Science, and Embase for eligible randomized controlled trials up to December 2021. Clinical trials reporting thyroid AEs including hypothyroidism, hyperthyroidism, and thyroiditis were enrolled. The I2 statistic was also calculated to quantify the heterogeneity. Data were evaluated as risk ratio (RR) and corresponding 95%CIs. A total of 10 randomized clinical trials involving 6154 patients were included in this meta-analysis. ICI application was found to have a statistically significant higher risk of all grade hypothyroidism (RR, 7.03; P < 0.0001), hyperthyroidism (RR, 4.88; P < 0.0001), and thyroiditis (RR, 6.58; P = 0.0014) compared with the chemotherapy group. Moreover, we demonstrated that second-line therapy significantly increased the risk of all-grade hypothyroidism (RR, 7.03 [95%CI, 4.69-10.55]) and hyperthyroidism (RR, 4.88 [95%CI, 3.11-7.65]). Our meta-analysis manifested that regimens with ICIs may significantly increase all grades of hypothyroidism, hyperthyroidism, and thyroiditis. ICIs may induce the occurrence and exacerbation of endocrine AEs compared with chemotherapy.

Keywords: CTLA-4 inhibitors; PD-1/PD-L1 inhibitors; non-small cell lung cancer; thyroid adverse events.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Humans
  • Hyperthyroidism* / chemically induced
  • Hyperthyroidism* / drug therapy
  • Hypothyroidism* / chemically induced
  • Hypothyroidism* / drug therapy
  • Immune Checkpoint Inhibitors / adverse effects
  • Lung Neoplasms* / drug therapy
  • Randomized Controlled Trials as Topic
  • Thyroid Diseases* / chemically induced

Substances

  • Immune Checkpoint Inhibitors