Hypothyroidism Induced by Immune Checkpoint Inhibitors Combined with Antiangiogenic Agents is Associated with Higher Body Mass Index

Overview

Journal J Thorac Dis

Publisher AME Publishing Company

Specialty Pulmonary Medicine

Date 2023 May 17

PMID 37197523

Authors

Xinyue Wang

Xiuqiong Chen

Jing Zhou

Richeng Jiang

Affiliations

Soon will be listed here.

Abstract

Background: Recent studies have reported that the combination of immune checkpoint inhibitors (ICIs) and antiangiogenic agents could be a promising therapeutic strategy for advanced non-small cell lung cancer (NSCLC). However, both ICIs and antiangiogenic agents are associated with endocrine dysfunctions, mainly hypothyroidism. The risk of hypothyroidism is potentially increased with the combination of ICIs and antiangiogenic agents. This study aimed to investigate the incidence and risk factors of hypothyroidism in patients receiving combination therapy.

Methods: We performed a retrospective cohort study of advanced NSCLC patients treated with ICIs and antiangiogenic agents at Tianjin Medical University Cancer Institute & Hospital from July 1, 2019, to December 31, 2021. Patients with normal thyroid function at baseline were enrolled, and information on the patients' characteristics before receiving combination therapy, including body mass index (BMI) and laboratory data, was obtained.

Results: Among the 137 enrolled patients, 39 (28.5%) developed new-onset hypothyroidism, and 20 (14.6%) developed overt hypothyroidism. The incidence of hypothyroidism was significantly higher in obese patients than in patients with a low to normal BMI (P<0.001). Obese patients also had a higher incidence of overt hypothyroidism (P=0.016). Univariate logistic regression showed that BMI as a continuous variable was a significant risk factor for hypothyroidism [odds ratio (OR) 1.24, 95% confidence interval (CI): 1.10-1.42, P<0.001] and overt hypothyroidism (OR 1.17, 95% CI: 1.01-1.38, P=0.039). Multivariate logistic regression revealed that only BMI (OR 1.36, 95% CI: 1.16-1.61, P<0.001) and age (OR 1.08, 95% CI: 1.02-1.14, P=0.006) were significant risk factors for treatment-related hypothyroidism.

Conclusions: The risk of hypothyroidism in patients receiving a combination of ICIs and antiangiogenic therapy is manageable, and a higher BMI is associated with a significantly increased risk of hypothyroidism. Therefore, clinicians should be aware of the development of hypothyroidism in obese advanced NSCLC patients during the administration of ICIs combined with antiangiogenic agents.

Citing Articles

Exploring risk factors for endocrine-related immune-related adverse events: Insights from meta-analysis and Mendelian randomization.

Quan L, Liu J, Wang Y, Yang F, Yang Z, Ju J Hum Vaccin Immunother. 2024; 20(1):2410557.

PMID: 39377304 PMC: 11469449. DOI: 10.1080/21645515.2024.2410557.

References

Ong K, Kuh D, Pierce M, Franklyn J . Childhood weight gain and thyroid autoimmunity at age 60-64 years: the 1946 British birth cohort study. J Clin Endocrinol Metab. 2013; 98(4):1435-42. PMC: 3651609. DOI: 10.1210/jc.2012-3761. View

Kobayashi T, Iwama S, Yasuda Y, Okada N, Tsunekawa T, Onoue T . Patients With Antithyroid Antibodies Are Prone To Develop Destructive Thyroiditis by Nivolumab: A Prospective Study. J Endocr Soc. 2018; 2(3):241-251. PMC: 5836529. DOI: 10.1210/js.2017-00432. View

Pang L, Gan J, Huang Y, Liao J, Zhuang W, Ali W . Role of antiangiogenic agents in first-line treatment for advanced NSCLC in the era of immunotherapy. BMC Cancer. 2023; 23(1):72. PMC: 9862794. DOI: 10.1186/s12885-022-10446-1. View

Cao Y . VEGF-targeted cancer therapeutics-paradoxical effects in endocrine organs. Nat Rev Endocrinol. 2014; 10(9):530-9. DOI: 10.1038/nrendo.2014.114. View

Kaaks R, Kuhn T . Epidemiology: obesity and cancer--the evidence is fattening up. Nat Rev Endocrinol. 2014; 10(11):644-5. DOI: 10.1038/nrendo.2014.168. View

Zhai X, Zhang L, Chen L, Lian X, Liu C, Shi B . An Age-Specific Serum Thyrotropin Reference Range for the Diagnosis of Thyroid Diseases in Older Adults: A Cross-Sectional Survey in China. Thyroid. 2018; 28(12):1571-1579. DOI: 10.1089/thy.2017.0715. View

Dote S, Yamaguchi D, Hira D, Noda S, Kobayashi Y, Terada T . Thyroid Dysfunction Related to the Antiangiogenic VEGFR2-Binding Monoclonal Antibody Ramucirumab: A Series of 14 Cases and a Descriptive Study. Biol Pharm Bull. 2020; 43(4):752-756. DOI: 10.1248/bpb.b19-01071. View

Naik A, Monjazeb A, Decock J . The Obesity Paradox in Cancer, Tumor Immunology, and Immunotherapy: Potential Therapeutic Implications in Triple Negative Breast Cancer. Front Immunol. 2019; 10:1940. PMC: 6703078. DOI: 10.3389/fimmu.2019.01940. View

Gao L, Yang X, Yi C, Zhu H . Adverse Events of Concurrent Immune Checkpoint Inhibitors and Antiangiogenic Agents: A Systematic Review. Front Pharmacol. 2019; 10:1173. PMC: 6812341. DOI: 10.3389/fphar.2019.01173. View

10.

Cao H . Adipocytokines in obesity and metabolic disease. J Endocrinol. 2014; 220(2):T47-59. PMC: 3887367. DOI: 10.1530/JOE-13-0339. View

11.

Chu T, Zhong R, Zhong H, Zhang B, Zhang W, Shi C . Phase 1b Study of Sintilimab Plus Anlotinib as First-line Therapy in Patients With Advanced NSCLC. J Thorac Oncol. 2021; 16(4):643-652. DOI: 10.1016/j.jtho.2020.11.026. View

12.

Pollack R, Kagan M, Lotem M, Dresner-Pollak R . BASELINE TSH LEVEL IS ASSOCIATED WITH RISK OF ANTI-PD-1-INDUCED THYROID DYSFUNCTION. Endocr Pract. 2019; 25(8):824-829. DOI: 10.4158/EP-2018-0472. View

13.

Weinstein A, Gordon R, Kasler M, Burke M, Ranjan S, Hodgetts J . Understanding and Managing Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors in Patients With Advanced Melanoma. J Adv Pract Oncol. 2018; 8(1):58-72. PMC: 5995532. DOI: 10.6004/jadpro.2017.8.1.5. View

14.

Labadzhyan A, Wentzel K, Hamid O, Chow K, Kim S, Piro L . Endocrine Autoantibodies Determine Immune Checkpoint Inhibitor-induced Endocrinopathy: A Prospective Study. J Clin Endocrinol Metab. 2022; 107(7):1976-1982. PMC: 9202695. DOI: 10.1210/clinem/dgac161. View

15.

Kang C, Liu J, Zheng Y, Wang X, Yang L, Qiu S . Association of high BMI with subclinical hypothyroidism in young, first-episode and drug-naïve patients with major depressive disorder: a large-scale cross-sectional study. Eur Arch Psychiatry Clin Neurosci. 2022; 273(1):183-190. DOI: 10.1007/s00406-022-01415-7. View

16.

Song Y, Fu Y, Xie Q, Zhu B, Wang J, Zhang B . Anti-angiogenic Agents in Combination With Immune Checkpoint Inhibitors: A Promising Strategy for Cancer Treatment. Front Immunol. 2020; 11:1956. PMC: 7477085. DOI: 10.3389/fimmu.2020.01956. View

17.

Reck M, Mok T, Nishio M, Jotte R, Cappuzzo F, Orlandi F . Atezolizumab plus bevacizumab and chemotherapy in non-small-cell lung cancer (IMpower150): key subgroup analyses of patients with EGFR mutations or baseline liver metastases in a randomised, open-label phase 3 trial. Lancet Respir Med. 2019; 7(5):387-401. DOI: 10.1016/S2213-2600(19)30084-0. View

18.

Chen S, Wei H, Zhao W, Jiang W, Ning R, Zhou S . PD-1/PD-L1 inhibitors plus anti-angiogenic agents with or without chemotherapy versus PD-1/PD-L1 inhibitors plus chemotherapy as second or later-line treatment for patients with advanced non-small cell lung cancer: A real-world retrospective cohort.... Front Immunol. 2022; 13:1059995. PMC: 9767946. DOI: 10.3389/fimmu.2022.1059995. View

19.

Bianchini F, Kaaks R, Vainio H . Overweight, obesity, and cancer risk. Lancet Oncol. 2002; 3(9):565-74. DOI: 10.1016/s1470-2045(02)00849-5. View

20.

Abdel-Rahman O, Fouad M . Risk of thyroid dysfunction in patients with solid tumors treated with VEGF receptor tyrosine kinase inhibitors: a critical literature review and meta analysis. Expert Rev Anticancer Ther. 2014; 14(9):1063-73. DOI: 10.1586/14737140.2014.929501. View