ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1606599
This article is part of the Research TopicCommunity Series in Immune Tolerance Dual Role: Advancements in Cancer and Autoimmune Diseases, Volume IIView all articles
Reporting of immune-related adverse events (irAEs) in US Food and Drug Administration (FDA) approvals of immune checkpoint inhibitors
Provisionally accepted
- 1Washington University in St. Louis, St. Louis, United States
- 2The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States
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Background: Predicting the occurrence of immune-related adverse events (irAEs) related to immune checkpoint inhibitors (ICI) is complex. Monitoring of irAEs is critical as toxicities cause morbidity and impact quality of life. Thus, we systematically evaluated the patterns and consistency of irAEs reporting in trials leading to US Food and Drug Administration (FDA) ICI approvals. Methods: We evaluated 75 primary articles from 2011-2021. The authors independently collected data regarding reporting frequency as a binary classification of reported versus not reported and irAE frequency of 24 irAEs classified by the National Comprehensive Cancer Network Version 1.2024 guidelines. Reporting trends and irAE events were analyzed by study year, phase, primary tumor type, and monotherapy versus combination therapy. Results: Across the irAEs evaluated, 42% were reported in less than 33% of the trials, 17% were reported in 34-66% of trials, and 42% were reported in 67-100% of trials. The most frequently reported irAEs included diarrhea/colitis (100%), fatigue (99%), and maculopapular rash (93%). Some infrequently reported irAEs included myocarditis (21%), uveitis (17%), and aseptic meningitis (4%). Additionally, certain organ systems were more frequently reported, including gastroenterology (100%) and endocrine (97%), while others, including cardiology (21%) and ophthalmology (17%), were less frequently reported. The reporting of rarer irAEs significantly increased over time. Conclusion: Our study demonstrated significant inconsistencies in irAE reporting in the primary literature of trials associated with FDA approvals, particularly for rarer irAEs. Efforts to standardize irAE reporting from clinical trials in the primary literature are needed for more consistent dissemination of information.
Keywords: immuno-oncology, Toxicity, Immune-related adverse events, immune checkpoint inhibitors, trial reporting, Morbidity
Received: 05 Apr 2025; Accepted: 28 Jul 2025.
Copyright: © 2025 Tapiavala, Luo, Shenouda, Patel and Davis. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Andrew Davis, Washington University in St. Louis, St. Louis, United States
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