免疫治疗肺癌诱发甲状腺功能异常的研究进展

doi:10.19401/j.cnki.1007-3639.2023.07.008

中国癌症杂志 ›› 2023, Vol. 33 ›› Issue (7): 701-706.doi: 10.19401/j.cnki.1007-3639.2023.07.008

免疫治疗肺癌诱发甲状腺功能异常的研究进展

张皓婷¹(), 郑静², 傅梦姣², 周建英²()

1.浙江大学医学院附属第四医院呼吸与危重症医学科，浙江大学国际健康医学研究院，浙江金华 322000
2.浙江大学医学院附属第一医院呼吸与危重症医学科，浙江杭州 310003

收稿日期:2022-10-08 修回日期:2022-11-24 出版日期:2023-07-30 发布日期:2023-08-10
通信作者: 周建英（ORCID: 0000-0002-8924-935X），硕士，主任医师，浙江大学附属一院呼吸与危重症医学科名誉主任。
作者简介:张皓婷（ORCID: 0000-0001-9986-712X），硕士。
基金资助:
浙江省科学技术厅重点研发计划(2019C03042)

Research progress on thyroid dysfunction induced by immunotherapy for lung cancer

ZHANG Haoting¹(), ZHENG Jing², FU Mengjiao², ZHOU Jianying²()

1. Department of Respiratory and Critical Care Medicine, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, International Institutes of Medicine, Zhejiang University, Jinhua 322000, Zhejiang Province, China
2. Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China

Received:2022-10-08 Revised:2022-11-24 Published:2023-07-30 Online:2023-08-10
Contact: ZHOU Jianying.

摘要/Abstract

摘要：

免疫检查点抑制剂[主要是程序性死亡-1/程序性死亡配体-1（programmed death-1/programmed death ligand-1，PD-1/PD-L1）抑制剂]已经逐渐成为晚期肺癌最具有前景的治疗手段。但临床医师对于免疫相关不良反应仍缺乏足够认识，免疫相关甲状腺功能异常（immune-related thyroid dysfunction，irTD）作为常见的免疫相关不良反应之一，严重时可能会危及生命。本文从发病率、发病机制、预测生物标志物及治疗等方面对PD-1/PD-L1抑制剂治疗肺癌诱发的甲状腺功能异常进行探讨。

Abstract:

Immune checkpoint inhibitors [mainly programmed death-1/programmed death ligand-1 (PD-1/PD-L1) inhibitors] have emerged as the most promising therapy in lung cancer treatment. However, clinicians still lack sufficient knowledge about immune-related adverse events. Immune-related thyroid dysfunction (irTD), one of the common immune-related adverse events, can be life-threatening in severe cases. This article discussed the thyroid dysfunction induced by PD-1/PD-L1 inhibitors in the treatment of lung cancer from the aspects of the incidence, pathogenesis, predictive biomarkers and treatment of irTD.

Key words: Immune-related thyroid dysfunction, Immune checkpoint inhibitors, Programmed death-1/programmed death ligand-1 inhibitors, Lung cancer

中图分类号:

R734.2

张皓婷, 郑静, 傅梦姣, 周建英. 免疫治疗肺癌诱发甲状腺功能异常的研究进展[J]. 中国癌症杂志, 2023, 33(7): 701-706.

ZHANG Haoting, ZHENG Jing, FU Mengjiao, ZHOU Jianying. Research progress on thyroid dysfunction induced by immunotherapy for lung cancer[J]. China Oncology, 2023, 33(7): 701-706.

图/表 1

表1

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免疫治疗肺癌诱发甲状腺功能异常的研究进展

Research progress on thyroid dysfunction induced by immunotherapy for lung cancer

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Clinical trial	Histological subtype	Case N	Treatment	Incidence of irTD all grade/%			Incidence of irTD grade 3%-5/%
Clinical trial	Histological subtype	Case N	Treatment	Hypo-thyroidism	Hyper-thyroidism	Thyroiditis	Hypo-thyroidism	Hyper-thyroidism	Thyroiditis
Checkmate-057^[3]	Non-squamous NSCLC	292	Nivolumab	7.0	1.0	0.3	0.0	0.0	0.0
Checkmate-017^[4]	Squamous NSCLC	135	Nivolumab	4.0	NA	NA	0.0	NA	NA
Keynote-024^[9]	NSCLC	154	Pembrolizumab	9.1	7.8	2.6	0.0	0.0	0.0
Checkmate-026^[8]	NSCLC	267	Nivolumab	6.4	NA	NA	0.0	NA	NA
Keynote-042^[5]	NSCLC	636	Pembrolizumab	12.0	6.0	2.0	0.2	0.2	0.0
Keynote-042^[11]	NSCLC	128	Pembrolizumab	11.7	5.5	1.6	0.0	0.8	0.0
CheckMate 078^[10]	NSCLC	337	Nivolumab	4.0	3.0	0.3	0.0	0.0	0.0
Antonia, et al^[12]	NSCLC	476	Durvalumab	9.5	2.7	NA	0.2	0.0	NA
JAVELIN Lung 200^[13]	NSCLC	396	Avelumab	5.0	1.0	0.3	0.3	NA	NA
Keynote-407^[17]	Squamous NSCLC	278	Pembrolizumab + carboplatin + nab-paclitaxel	7.9	7.2	1.1	0.4	0.4	0.4
Keynote-189^[14]	Non-squamous NSCLC	405	Pembrolizumab + platinum + pemetrexed	6.7	4.0	0.2	0.5	0.0	0.0
IMpower130^[18]	Non-squamous NSCLC	473	Atezolizumab + carboplatin + nab-paclitaxel	11.2	4.9	NA	0.4	0.2	NA
IMpower132^[15]	Non-squamous NSCLC	292	Atezolizumab + carboplatin/cisplatin + pemetrexed	8.2	2.4	NA	0.3	0.3	NA
CASPIAN^[16]	ES-SCLC	265	Durvalumab + platinum + etoposide	9.0	8.0	NA	0.0	0.0	NA
IMpower133^[20]	ES-SCLC	198	Atezolizumab + carboplatin + etoposide	12.6	5.6	NA	0.0	0.0	NA
Checkmate-227^[7]	NSCLC	396	Nivolumab + ipilimumab	11.6	NA	NA	0.3	NA	NA
		396	Nivolumab	6.4	NA	NA	0.3	NA	NA
Checkmate-9LA^[21]	NSCLC	358	Nivolumab + ipilimumab + platinum	16.0	NA	NA	0.3	NA	NA
Keynote-598^[19]	NSCLC	282	Pembrolizumab + ipilimumab	15.2	8.9	1.8	0.4	0.4	0.4
Keynote-598^[19]	NSCLC	281	Pembrolizumab	12.1	6.0	1.1	0.4	0.0	0.0
Checkmate-032^[6]	SCLC	96	Nivolumab + ipilimumab	8.3	7.3	NA	0.0	1.0	NA
Checkmate-032^[6]	SCLC	147	Nivolumab	4.1	2.0	NA	0.0	0.0	NA

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