Immune related thyroidopathy as a prognostic factor for survival in patients with various cancer types receiving immune checkpoint inhibitor therapy
Zherebchikova K.Yu., Poddubskaya E.V., Bondarenko A.P., Vilensky A.A., Sych Yu.P., Fadeev V.V.
Background: Immune related thyroid disorders (IMTDs) are among the most common endocrine side effects associated with immune checkpoint inhibitor (ICI) therapy. Several studies have demonstrated a possible association with more favorable cancer outcomes; however, these data remain heterogeneous and may depend on the tumor type.
Objective: Evaluation of the association of IVTD development with overall survival (OS) and progression-free survival (PFS) in patients with non-small cell lung cancer, melanoma, gastric cancer, and hepatocellular carcinoma receiving immune checkpoint inhibitor therapy.
Materials and methods: A multicenter, prospective, observational cohort study was conducted. The analytical sample included 182 patients: 114 with non-small cell lung cancer, 32 with melanoma, 25 with gastric cancer, and 11 with hepatocellular carcinoma. Thyroid function was monitored before the start of ICI therapy and every 4 weeks thereafter. OS and PFS were estimated using the Kaplan-Meier method; groups were compared using the log-rank test and univariate Cox proportional hazards models.
Results: IMTDs were detected in 41 (22.5%) of 182 patients and developed, on average, 7.75±2.42 weeks after the start of therapy. In a subgroup analysis, the development of thyroid disorders was associated with higher OS and PFS in patients with non-small cell lung cancer and gastric cancer. No statistically significant association between thyroid disorders and survival was found in patients with melanoma and hepatocellular carcinoma.
Conclusion: IMTDs during ICI therapy was not associated with more favorable survival outcomes in all nosological subgroups. The most significant association was found in patients with non-small cell lung cancer and gastric cancer, while no statistically significant association was found for melanoma and hepatocellular carcinoma. These results suggest that thyroidopathy may be a potential clinical marker for immunotherapy efficacy in certain patient groups.
For citations: Zherebchikova K.Yu., Poddubskaya E.V., Bondarenko A.P., Vilensky A.A., Sych Yu.P., Fadeev V.V. Immune related thyroidopathy as a prognostic factor for survival in patients with various cancer types receiving immune checkpoint inhibitor therapy. Pharmateca. 2026;33(2):118-126. (In Russ.). DOI: https://dx.doi.org/10.18565/pharmateca.2026.2.118-126
Authors’ contribution: K.Yu. Zherebchikova – developed the concept and design of the study. K.Yu. Zherebchikova, A.A. Vilensky, A.P. Bondarenko, E.V. Poddubskaya – collected and processed the data. Zherebchikova K.Yu. – created the electronic database, performed statistical processing, analyzed the obtained results, and wrote the main text of the manuscript. Sych Yu.P., Fadeev V.V. – provided scientific supervision of the study and edited the manuscript. All authors approved the final version of the publication.
Conflicts of interest: The authors confirm that they have no conflicts of interest to declare.
Funding: The study was conducted without any sponsorship.
Ethical Approval: The study protocol was reviewed and approved at a meeting of the local ethics committee of the Federal State Autonomous Educational Institution of Higher Education, I.M. Sechenov First Moscow State Medical University (Sechenov University) (protocol No. 03-19 dated February 13, 2019).
Patient Consent for Publication: All patients provided informed consent for the publication of their data.
Authors’ Data Sharing Statement: The data supporting the findings of this study are available upon request from the corresponding author after approval from the principal investigator.
Keywords
immune checkpoint inhibitors
thyroid gland
thyroiditis
overall survival
progression-free survival
About the Authors
K.Yu. Zherebchikova, Teaching Assistant, Department of Endocrinology No. 1, N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia; k.y.zherebchikova@gmail.com, ORCID: https://orcid.org/0000-0003-0292-5907 (corresponding author)E.V. Poddubskaya, Cand. Sci. (Med.), Deputy Director of the Clinical Center for Oncology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia; ORCID: https://orcid.org/0000-0001-6476-6337
A.P. Bondarenko, Head of the Day Hospital, VitaMed LLC, Moscow, Russia; ORCID: https://orcid.org/0000-0001-9745-2916
A.A. Vilensky, Head of the Department of Antitumor Drug Therapy, Research Center, Lomonosov Moscow State University, Moscow, Russia; ORCID: https://orcid.org/0000-0002-3094-7671
Yu.P. Sych, Cand. Sci. (Med.), Associate Professor, Department of Endocrinology No. 1, N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia; ORCID: https://orcid.org/0000-0002-7000-0095
V.V. Fadeev, Dr. Sci. (Med.), Professor, Corresponding Member of the Russian Academy of Medical Sciences, Professor, Department of Internal Medicine, Faculty of Fundamental Medicine, Moscow Scientific Institute of Occupational Medicine, Lomonosov Moscow State University, Moscow, Russia; ORCID: https://orcid.org/0000-0002-2504-7468
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