Immune-Related Adverse Event-Related Adrenal Insufficiency Mediates Immune Checkpoint Inhibitors Efficacy in Cancer Treatment

IF 2.5 4区医学 Q3 ONCOLOGY Cancer Management and Research Pub Date : 2024-03-14 DOI:10.2147/cmar.s444916

Shasha Zhang, Jianhua Wu, Yue Zhao, Jingjing Zhang, Xiaoyun Zhang, Chensi Wu, Zhidong Zhang, Zhanjun Guo

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引用次数: 0

Abstract

Purpose: Immune checkpoint inhibitors (ICIs) have significantly improved the outcomes of patients with cancer; however, these agents may initiate immune-related adverse events (irAEs). Previous studies have demonstrated a robust correlation between disease prognosis and the occurrence of irAEs, specifically skin or endocrine irAEs. Herein, we aimed to evaluate the correlation between irAE-related adrenal insufficiency (AI) and ICI treatment efficacy.
Patients and methods: Patients diagnosed with gastrointestinal, respiratory, head and neck, urological, skin and gynecologic cancers treated with anti-programmed cell death 1 (PD-1)/anti-programmed cell death ligand 1 (PD-L1) antibody as monotherapy or combined therapy (combined with chemotherapy or targeted therapy) were divided into irAE-A (patients with irAE-related AI), irAE-B (patients with other irAEs) and non-irAE groups. Immunotherapy efficacy was assessed based on the disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Survival probabilities were estimated using the Kaplan–Meier method with the log–rank test.
Results: Of the 192 patients enrolled in our study, 17 developed irAE-related AI and 83 developed other irAEs. The DCR of the irAE-A and irAE-B groups were higher than that of the non-irAE group (P< 0.05). Multiple extended Cox regression analyses showed that irAE status (irAE-A vs non-irAE, P=0.008; irAE-B vs non-irAE, P=0.020), Eastern Cooperative Oncology Group (ECOG) status (P=0.045), tumor-node-metastasis (TNM) stage (P=0.000), and treatment line (P=0.002) were independent predictors of PFS. Contrarily, irAE status (irAE-A vs non-irAE, P=0.009; irAE-B vs non-irAE, P=0.013), ECOG status (P=0.007), TNM stage (P=0.035), treatment line (P=0.001) and treatment modality (P=0.008) were independent predictors for OS.
Conclusion: IrAE-related AI was significantly associated with ICI treatment efficacy in patients with cancer, which could be a potentially predictable marker. Due to the destruction of adrenal tissue by T cells with enhanced activity, AI reflects enhanced T cell activity to some extent.

Keywords: endocrine adverse event, malignancies, monoclonal antibody therapy, immune-related side effects, treatment efficacy

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与免疫相关的不良事件--肾上腺功能不全介导了免疫检查点抑制剂在癌症治疗中的疗效

目的：免疫检查点抑制剂（ICIs）大大改善了癌症患者的预后；然而，这些药物可能引发免疫相关不良事件（irAEs）。以往的研究表明，疾病预后与irAEs（尤其是皮肤或内分泌irAEs）的发生之间存在密切的相关性。在此，我们旨在评估与irAE相关的肾上腺功能不全（AI）与ICI疗效之间的相关性：将胃肠道癌、呼吸系统癌、头颈部癌、泌尿系统癌、皮肤癌和妇科癌症患者分为irAE-A组（irAE相关肾上腺功能不全患者）、irAE-B组（其他irAEs患者）和非irAE组，使用抗程序性细胞死亡1（PD-1）/抗程序性细胞死亡配体1（PD-L1）抗体进行单药治疗或联合治疗（联合化疗或靶向治疗）。免疫疗法的疗效根据疾病控制率（DCR）、无进展生存期（PFS）和总生存期（OS）进行评估。采用卡普兰-梅耶法和对数秩检验估算生存概率：在192例参与研究的患者中，17例出现了与虹膜AE相关的AI，83例出现了其他虹膜AE。irAE-A组和irAE-B组的DCR高于非irAE组（P< 0.05）。多重扩展 Cox 回归分析显示，irAE 状态（irAE-A vs 非 irAE，P=0.008；irAE-B vs 非 irAE，P=0.020）、东部合作肿瘤学组（ECOG）状态（P=0.045）、肿瘤结节-转移（TNM）分期（P=0.000）和治疗线（P=0.002）是 PFS 的独立预测因素。相反，irAE状态（irAE-A vs nonirAE，P=0.009；irAE-B vs nonirAE，P=0.013）、ECOG状态（P=0.007）、TNM分期（P=0.035）、治疗线（P=0.001）和治疗方式（P=0.008）是OS的独立预测因素：结论：IrAE相关的AI与癌症患者的ICI疗效明显相关，这可能是一个潜在的可预测标志物。关键词：内分泌不良事件；恶性肿瘤；单克隆抗体治疗；免疫相关副作用；疗效

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来源期刊

Cancer Management and Research Medicine-Oncology

CiteScore

7.40

自引率

0.00%

发文量

448

审稿时长

16 weeks

期刊介绍： Cancer Management and Research is an international, peer reviewed, open access journal focusing on cancer research and the optimal use of preventative and integrated treatment interventions to achieve improved outcomes, enhanced survival, and quality of life for cancer patients. Specific topics covered in the journal include: ◦Epidemiology, detection and screening ◦Cellular research and biomarkers ◦Identification of biotargets and agents with novel mechanisms of action ◦Optimal clinical use of existing anticancer agents, including combination therapies ◦Radiation and surgery ◦Palliative care ◦Patient adherence, quality of life, satisfaction The journal welcomes submitted papers covering original research, basic science, clinical & epidemiological studies, reviews & evaluations, guidelines, expert opinion and commentary, and case series that shed novel insights on a disease or disease subtype.