Thyroid dysfunction during PD‑1 inhibitor treatment in patients with cancer: Incidence and association with progression‑free survival

Wu,Yanfei; Wang,Zhi; Bai,Hongxia; Gao,Yan

doi:10.3892/ol.2022.13429

Thyroid dysfunction during PD‑1 inhibitor treatment in patients with cancer: Incidence and association with progression‑free survival

Authors:
- Yanfei Wu
- Zhi Wang
- Hongxia Bai
- Yan Gao
View Affiliations

Affiliations: Department of Pathology, Navy Medical Center of People Liberation Army, Naval Medical University, Shanghai 200433, P.R. China, Department of Nuclear Radiation Injury Protection and Treatment, Navy Medical Center of People Liberation Army, Naval Medical University, Shanghai 200433, P.R. China, Department of Pulmonary and Critical Care Medicine, Baotou Central Hospital, Baotou, Inner Mongolia Autonomous Region 014040, P.R. China, Department of Nuclear Medicine, Baotou Tumor Hospital, Baotou, Inner Mongolia Autonomous Region 014030, P.R. China
Published online on: July 13, 2022 https://doi.org/10.3892/ol.2022.13429
Article Number: 309
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The use of programmed cell death‑1 (PD‑1) inhibitors has recently been approved in China. As a consequence, the identification of relevant prognostic markers that can assess the efficacy of these compounds is required. Therefore, the present study aimed to explore the incidence of thyroid dysfunction and its ability to predict progression‑free survival (PFS) in Chinese patients with cancer who received PD‑1 inhibitor treatment. Data from 72 patients with cancer who received treatment with PD‑1 inhibitors alone or in combination with chemotherapy or targeted drugs were analyzed. Moreover, the expression levels of free triiodothyronine, thyroxine, and thyrotropin during treatment were assessed to evaluate thyroid dysfunction. A total of 26 (36.1%) patients who had received PD‑1 inhibitors developed thyroid dysfunction. Specifically, the incidence of thyroid dysfunction was 35.6% in patients with lung cancer, 25.0% in patients with malignant melanoma, and 46.7% in patients with other types of cancer. In addition, the median PFS was 7.0 (95% confidence interval, 4.9‑9.1) months, whereas the 1‑ and 2‑year PFS rates were 35.1 and 26.2%, respectively. Generally, patients with thyroid dysfunction exhibited longer PFS compared with those without thyroid dysfunction (P=0.001). Subgroup analyses were subsequently performed, which demonstrated that thyroid dysfunction was associated with longer PFS in patients with malignant melanoma (P=0.039) and other types of cancer (P=0.002), but not in those with lung cancer (P=0.083). These findings were noted in patients who received PD‑1 inhibitor monotherapy (P=0.003), but not PD‑1 inhibitor plus chemotherapy (P=0.172) or PD‑1 inhibitor plus targeted therapy (P=0.582). Finally, thyroid dysfunction [P=0.001; hazard ratio (HR)=0.260] and PD‑1 inhibitor monotherapy (P=0.015; HR=2.231) were identified as independent factors that could predict PFS. In conclusion, the present study demonstrated that thyroid dysfunction during PD‑1 inhibitor treatment could be used as a potential marker for the prognosis of favorable PFS in patients with cancer.

View Figures

View References

1	Jiang Y, Chen M, Nie H and Yuan Y: PD-1 and PD-L1 in cancer immunotherapy: Clinical implications and future considerations. Hum Vaccin Immunother. 15:1111–1122. 2019. View Article : Google Scholar : PubMed/NCBI
2	Ai L, Xu A and Xu J: Roles of PD-1/PD-L1 pathway: Signaling, cancer, and beyond. Adv Exp Med Biol. 1248:33–59. 2020. View Article : Google Scholar
3	Han Y, Liu D and Li L: PD-1/PD-L1 pathway: Current researches in cancer. Am J Cancer Res. 10:727–742. 2020.PubMed/NCBI
4	Kythreotou A, Siddique A, Mauri FA, Bower M and Pinato DJ: Pd-L1. J Clin Pathol. 71:189–194. 2018. View Article : Google Scholar
5	Ni JM and Ni AP: Landscape of PD-1/PD-L1 regulation and targeted immunotherapy. Chin Med Sci J. 33:174–182. 2018.PubMed/NCBI
6	Gou Q, Dong C, Xu H, Khan B, Jin J, Liu Q, Shi J and Hou Y: PD-L1 degradation pathway and immunotherapy for cancer. Cell Death Dis. 11:9552020. View Article : Google Scholar : PubMed/NCBI
7	Sun C, Mezzadra R and Schumacher TN: Regulation and function of the PD-L1 checkpoint. Immunity. 48:434–452. 2018. View Article : Google Scholar : PubMed/NCBI
8	Xie W, Medeiros LJ, Li S, Yin CC, Khoury JD and Xu J: PD-1/PD-L1 pathway and its blockade in patients with classic hodgkin lymphoma and non-hodgkin large-cell lymphomas. Curr Hematol Malig Rep. 15:372–381. 2020. View Article : Google Scholar : PubMed/NCBI
9	Wu X, Gu Z, Chen Y, Chen B, Chen W, Weng L and Liu X: Application of PD-1 blockade in cancer immunotherapy. Comput Struct Biotechnol J. 17:661–674. 2019. View Article : Google Scholar : PubMed/NCBI
10	Feng M, Xiong G, Cao Z, Yang G, Zheng S, Song X, You L, Zheng L, Zhang T and Zhao Y: PD-1/PD-L1 and immunotherapy for pancreatic cancer. Cancer Lett. 407:57–65. 2017. View Article : Google Scholar
11	Hayashi H and Nakagawa K: Combination therapy with PD-1 or PD-L1 inhibitors for cancer. Int J Clin Oncol. 25:818–830. 2020. View Article : Google Scholar
12	Salmaninejad A, Valilou SF, Shabgah AG, Aslani S, Alimardani M, Pasdar A and Sahebkar A: PD-1/PD-L1 pathway: Basic biology and role in cancer immunotherapy. J Cell Physiol. 234:16824–16837. 2019. View Article : Google Scholar
13	D'Andrea G, Lassalle S, Guevara N, Mograbi B and Hofman P: From biomarkers to therapeutic targets: The promise of PD-L1 in thyroid autoimmunity and cancer. Theranostics. 11:1310–1325. 2021. View Article : Google Scholar
14	Manolis AA, Manolis TA, Melita H and Manolis AS: Subclinical thyroid dysfunction and cardiovascular consequences: An alarming wake-up call? Trends Cardiovasc Med. 30:57–69. 2020. View Article : Google Scholar : PubMed/NCBI
15	Chalan P, Di Dalmazi G, Pani F, De Remigis A, Corsello A and Caturegli P: Thyroid dysfunctions secondary to cancer immunotherapy. J Endocrinol Invest. 41:625–638. 2018. View Article : Google Scholar
16	Osorio JC, Ni A, Chaft JE, Pollina R, Kasler MK, Stephens D, Rodriguez C, Cambridge L, Rizvi H, Wolchok JD, et al: Antibody-mediated thyroid dysfunction during T-cell checkpoint blockade in patients with non-small-cell lung cancer. Ann Oncol. 28:583–589. 2017. View Article : Google Scholar
17	Basak EA, van der Meer JWM, Hurkmans DP, Schreurs MWJ, Oomen-de Hoop E, van der Veldt AAM, Bins S, Joosse A, Koolen SLW, Debets R, et al: Overt thyroid dysfunction and anti-thyroid antibodies predict response to anti-PD-1 immunotherapy in cancer patients. Thyroid. 30:966–973. 2020. View Article : Google Scholar : PubMed/NCBI
18	Wolffenbuttel BHR, Wouters HJCM, Slagter SN, van Waateringe RP, Muller Kobold AC, van Vliet-Ostaptchouk JV, Links TP and van der Klauw MM: Thyroid function and metabolic syndrome in the population-based LifeLines cohort study. BMC Endocr Disord. 17:652017. View Article : Google Scholar : PubMed/NCBI
19	Sakakida T, Ishikawa T, Uchino J, Chihara Y, Komori S, Asai J, Narukawa T, Arai A, Kobayashi T, Tsunezuka H, et al: Clinical features of immune-related thyroid dysfunction and its association with outcomes in patients with advanced malignancies treated by PD-1 blockade. Oncol Lett. 18:2140–2147. 2019.
20	Endo K, Masatani T, Tsuji A, Kondo S, Wakisaka N, Murono S and Yoshizaki T: Thyroid dysfunction after intra-arterial chemotherapy for hypopharyngeal and laryngeal cancer. Auris Nasus Larynx. 42:231–234. 2015. View Article : Google Scholar : PubMed/NCBI
21	Breimer LH, Nousios P, Olsson L and Brunnström H: Immune checkpoint inhibitors of the PD-1/PD-L1-axis in non-small cell lung cancer: Promise, controversies and ambiguities in the novel treatment paradigm. Scand J Clin Lab Invest. 80:360–369. 2020. View Article : Google Scholar
22	Zhou Y, Xia R, Xiao H, Pu D, Long Y, Ding Z, Liu J and Ma X: Thyroid function abnormality induced by PD-1 inhibitors have a positive impact on survival in patients with non-small cell lung cancer. Int Immunopharmacol. 91:1072962021. View Article : Google Scholar
23	Chmielewska I, Dudzińska M, Szczyrek M, Świrska J, Wojas-Krawczyk K and Zwolak A: Do endocrine adverse events predict longer progression-free survival among patients with non-small-cell lung cancer receiving nivolumab? PLoS One. 16:e02574842021. View Article : Google Scholar : PubMed/NCBI
24	Frelau A, Jali E, Campillo-Gimenez B, Pracht M, Porneuf M, Dinulescu M, Edeline J, Boussemart L and Lesimple T: Prognostic impact of thyroid dysfunctions on progression-free survival in patients with metastatic melanoma treated with anti-PD-1 antibodies. Melanoma Res. 31:208–217. 2021. View Article : Google Scholar : PubMed/NCBI