Hye In Kim, Won Gu Kim, Mijin Kim, Nak Gyeong Ko, Mihyeon Jin, Hyun Ae Jung, Jong-Mu Sun, Jin Seok Ahn, Myung-Ju Ahn, Yoon-La Choi, Min Ji Jeon, Tae Yong Kim, Won Bae Kim, Sang-We Kim, Dae Ho Lee, Se Jin Jang, Sun Wook Kim, Jae Hoon Chung, Tae Hyuk Kim, Se-Hoon Lee
{"title":"甲状腺irAE和PD-L1阳性在预测非小细胞肺癌患者PD-1阻断剂疗效中的生物标记作用。","authors":"Hye In Kim, Won Gu Kim, Mijin Kim, Nak Gyeong Ko, Mihyeon Jin, Hyun Ae Jung, Jong-Mu Sun, Jin Seok Ahn, Myung-Ju Ahn, Yoon-La Choi, Min Ji Jeon, Tae Yong Kim, Won Bae Kim, Sang-We Kim, Dae Ho Lee, Se Jin Jang, Sun Wook Kim, Jae Hoon Chung, Tae Hyuk Kim, Se-Hoon Lee","doi":"10.1007/s00262-024-03852-w","DOIUrl":null,"url":null,"abstract":"<p><p>Thyroid immune-related adverse events (irAEs) are associated with programmed cell death protein 1 (PD-1) blockade efficacy in non-small cell lung cancer (NSCLC). However, their independence from PD-L1 expression and quantitative impact on predicting PD-1 blockade efficacy remain unexplored. This multicenter, retrospective, longitudinal study from Korea included 71 metastatic NSCLC patients who underwent PD-L1 expression and thyroid function testing during PD-1 blockade. Disease progression by the Response Evaluation Criteria for Solid Tumors was the main outcome. Three-stage analyses were performed: (1) multivariate Cox regression models adjusted for PD-L1 expression according to thyroid irAEs; (2) subgroup analyses; (3) regrouping and comparing predictivity of current and alternative staging. Patients with thyroid irAE + exhibited a longer progression-free survival [7/20 vs. 34/51, adjusted HR 0.19 (0.07-0.47); P < 0.001] than those with thyroid irAE-, independent of PD-L1 expression; the results remained across most subgroups without interaction. The three groups showed different adjusted HR for disease progression (Group 1: PD L1 + and thyroid irAE + ; Group 2: PD-L1 + or thyroid irAE + : 5.08 [1.48-17.34]; Group 3: PD-L1- and thyroid irAE- : 30.49 [6.60-140.78]). Alternative staging (Group 1 in stage IVB → stage IVA; Group 3 in stage IVA → stage IVB) improved the prognostic value (PVE: 21.7% vs. 6.44%; C-index: 0.706 vs. 0.617) compared with the 8th Tumor-Node-Metastasis staging. 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引用次数: 0
摘要
甲状腺免疫相关不良事件(irAEs)与程序性细胞死亡蛋白1(PD-1)在非小细胞肺癌(NSCLC)中的阻断疗效有关。然而,它们与 PD-L1 表达的独立性以及对预测 PD-1 阻断疗效的定量影响仍未得到探讨。这项来自韩国的多中心回顾性纵向研究纳入了71例转移性NSCLC患者,他们在PD-1阻断治疗期间接受了PD-L1表达和甲状腺功能检测。根据实体瘤反应评估标准得出的疾病进展是主要结果。分析分为三个阶段:(1)根据甲状腺irAE调整PD-L1表达的多变量Cox回归模型;(2)亚组分析;(3)重新分组并比较当前分期和替代分期的预测性。甲状腺irAE+患者的无进展生存期更长[7/20 vs. 34/51,调整后HR 0.19 (0.07-0.47); P
Biomarker role of thyroid irAE and PD-L1 positivity in predicting PD-1 blockade efficacy in patients with non-small cell lung cancer.
Thyroid immune-related adverse events (irAEs) are associated with programmed cell death protein 1 (PD-1) blockade efficacy in non-small cell lung cancer (NSCLC). However, their independence from PD-L1 expression and quantitative impact on predicting PD-1 blockade efficacy remain unexplored. This multicenter, retrospective, longitudinal study from Korea included 71 metastatic NSCLC patients who underwent PD-L1 expression and thyroid function testing during PD-1 blockade. Disease progression by the Response Evaluation Criteria for Solid Tumors was the main outcome. Three-stage analyses were performed: (1) multivariate Cox regression models adjusted for PD-L1 expression according to thyroid irAEs; (2) subgroup analyses; (3) regrouping and comparing predictivity of current and alternative staging. Patients with thyroid irAE + exhibited a longer progression-free survival [7/20 vs. 34/51, adjusted HR 0.19 (0.07-0.47); P < 0.001] than those with thyroid irAE-, independent of PD-L1 expression; the results remained across most subgroups without interaction. The three groups showed different adjusted HR for disease progression (Group 1: PD L1 + and thyroid irAE + ; Group 2: PD-L1 + or thyroid irAE + : 5.08 [1.48-17.34]; Group 3: PD-L1- and thyroid irAE- : 30.49 [6.60-140.78]). Alternative staging (Group 1 in stage IVB → stage IVA; Group 3 in stage IVA → stage IVB) improved the prognostic value (PVE: 21.7% vs. 6.44%; C-index: 0.706 vs. 0.617) compared with the 8th Tumor-Node-Metastasis staging. Our study suggests thyroid irAEs and PD-L1 expression are independent biomarkers that improve predicting PD-1 blockade efficacy in NSCLC. Thyroid irAEs would be helpful to identify NSCLC patients who benefit from PD-1 blockade in early course of treatment.
期刊介绍:
Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions.
The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.