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


中文翻译：

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免疫相关不良事件相关肾上腺功能不全介导免疫检查点抑制剂在癌症治疗中的功效

目的：免疫检查点抑制剂（ICIs）显着改善癌症患者的预后；然而，这些药物可能会引发免疫相关不良事件（irAE）。先前的研究已证明疾病预后与 irAE（特别是皮肤或内分泌 irAE）的发生之间存在密切相关性。在此，我们的目的是评估 irAE 相关的肾上腺功能不全 (AI) 与 ICI 治疗效果之间的相关性。
患者和方法：被诊断患有胃肠道、呼吸道、头颈、泌尿、皮肤和妇科癌症的患者接受抗程序性细胞死亡 1 (PD-1)/抗程序性细胞死亡配体 1 (PD-L1) 抗体作为单一疗法的治疗或联合治疗（联合化疗或靶向治疗）分为irAE-A（患有irAE相关AI的患者）、irAE-B（患有其他irAE的患者）和非irAE组。根据疾病控制率（DCR）、无进展生存期（PFS）和总生存期（OS）评估免疫治疗疗效。使用 Kaplan-Meier 方法和对数秩检验估计生存概率。
结果：在参加我们研究的 192 名患者中，17 名患者出现了 irAE 相关的 AI，83 名患者出现了其他 irAE。irAE-A 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 与非 irAE，P = 0.008；irAE-B 与非 irAE，P = 0.020）、东部肿瘤合作组（ECOG）状态（P = 0.045）、肿瘤-淋巴结转移 (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 与非 irAE，P = 0.009；irAE-B 与非 irAE，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 AI 与癌症患者 ICI 治疗效果显着相关，这可能是一个潜在的可预测标志物。由于活性增强的T细胞对肾上腺组织的破坏，AI在一定程度上反映了T细胞活性的增强。

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, 治疗效果