Effects of immune checkpoint inhibitor associated endocrinopathies on cancer survival

Front Endocrinol (Lausanne). 2024 Apr 12:15:1369268. doi: 10.3389/fendo.2024.1369268. eCollection 2024.

Abstract

Objectives: Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs), of which endocrinopathies are common. We characterized endocrine and non-endocrine irAEs in cancer patients receiving ICIs, identified risk factors for their development and established whether endocrine and non-endocrine irAEs were differentially associated with improved cancer prognosis.

Design and methods: Single-center, retrospective cohort study of patients with advanced or metastatic solid tumors receiving at least one ICI treatment cycle (242 men, 151 women, median age 65 years). Main outcome measures were incidence of any irAE during the study period, overall survival and time to treatment failure.

Results: Non-endocrine irAEs occurred in 32% and endocrine irAEs in 12% of patients. Primary thyroid dysfunction was the most common endocrine irAE (9.5%) and the majority of endocrinopathies required permanent hormone replacement. Women had an increased risk of developing endocrine irAEs (p = 0.017). The biggest survival advantage occurred in patients who developed both endocrine and non-endocrine irAEs (overall survival: HR 0.16, CI 0.09-0.28). Time to treatment failure was also significantly improved in patients who developed endocrine irAEs (HR 0.49, CI 0.34 - 0.71) or both (HR 0.41, CI 0.25 - 0.64) but not in those who only developed non-endocrine irAEs.

Conclusions: Women may have increased risk of endocrine irAEs secondary to ICI treatment. This is the first study to compare the effects of endocrine irAEs with non-endocrine irAEs on survival. Development of endocrine irAEs may confer survival benefit in ICI treatment and future, prospective studies are needed to elucidate this.

Keywords: cancer; endocrinopathy; immune checkpoint inhibitor; immune related adverse effects (irAEs); survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Endocrine System Diseases* / chemically induced
  • Endocrine System Diseases* / epidemiology
  • Female
  • Humans
  • Immune Checkpoint Inhibitors* / adverse effects
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Male
  • Middle Aged
  • Neoplasms* / drug therapy
  • Neoplasms* / mortality
  • Prognosis
  • Retrospective Studies
  • Risk Factors
  • Survival Rate

Substances

  • Immune Checkpoint Inhibitors

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Institute for Health Research (NIHR), the NIHR Imperial Clinical Research Facility, and NIHR Imperial Biomedical Research Centre at Imperial College Healthcare NHS Trust. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. The Section of Endocrinology and Investigative Medicine is funded by grants from the UK Medical Research Council (MRC), Biotechnology and Biological Sciences Research Council, and NIHR. SM was supported by a Society for Endocrinology BES Student Registration Grant 2022. DJP is supported by grant funding from the Wellcome Trust Strategic Fund (PS3416), the Associazione Italiana per la Ricerca sul Cancro (AIRC MFAG 25697) and acknowledges grant support from the Cancer Treatment and Research Trust (CTRT) and The Foundation for Liver Research.