Introduction: Development of immune-related adverse events (irAEs) has been associated with enhanced efficacy with the use of immune checkpoint inhibitors (ICIs). It remains unknown whether such an association exists in advanced hepatocellular carcinoma (aHCC). This study aims to evaluate the association between irAEs and ICI efficacy in patients with aHCC. Methods: We performed a retrospective cohort study on patients with aHCC who received at least one dose of an ICI between May 2015 and November 2019 at the National Cancer Centre Singapore. The primary study objectives were to compare the overall survival (OS) and progression-free survival (PFS) between patients with and without irAEs. Complementary multivariable landmark analyses were performed at the 6-week and 12-week landmarks. Data cutoff was December 31, 2020. Results: One hundred and sixty-eight patients were included. Median age was 69 years, 85.7% were male, 57.7% had hepatitis B infection, 60.7% had ECOG 0, and 78.0% had Child-Pugh A liver cirrhosis. 82.7% received ICI monotherapy, while 17.3% received ICI in combination. Development and severity of irAE were correlated with survival. The median PFS for grade ≥3 irAE versus grades 1–2 irAE versus no irAE was 8.5 versus 3.6 versus 1.3 mths (p #x3c; 0.001). The median OS for grade ≥3 irAE versus grades 1–2 irAE versus no irAE was 26.9 versus 14.0 versus 4.6 mths (p #x3c; 0.001). Patients with ≥2 irAEs had a significantly longer OS on multivariable analysis (adjusted hazard ratio [aHR]0.35, p #x3c; 0.001). The presence of grade ≥3 irAEs was associated with a significantly longer OS on the multivariable analysis at the 6-week landmark (aHR0.34, p = 0.030) and 12-week landmark (aHR0.28, p = 0.011). The use of systemic corticosteroids in patients with irAE was associated with a trend toward a longer OS (20.7 vs. 14.3 mths, p = 0.064). Conclusion: Our study suggests that the presence of all-grade irAEs may be a potential prognostic biomarker in patients with aHCC treated with ICI. Patients with more severe irAEs and multisystem involvement have better prognosis. The prompt use of systemic corticosteroids to treat patients with irAEs is key to ensure the best long-term outcomes for these patients.
Liver Cancer

中文翻译：

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免疫相关不良事件对晚期肝细胞癌患者免疫检查点抑制剂疗效的影响

简介：免疫相关不良事件 (irAE) 的发生与使用免疫检查点抑制剂 (ICI) 提高疗效有关。目前尚不清楚这种关联是否存在于晚期肝细胞癌（aHCC）中。本研究旨在评估 irAE 与 aHCC 患者 ICI 疗效之间的关联。方法：我们对 2015 年 5 月至 2019 年 11 月期间在新加坡国家癌症中心接受至少一剂 ICI 的 aHCC 患者进行了一项回顾性队列研究。主要研究目标是比较有和没有 irAEs 患者的总生存期 (OS) 和无进展生存期 (PFS)。在 6 周和 12 周的地标处进行了互补的多变量地标分析。数据截止日期为 2020 年 12 月 31 日。结果：包括 168 名患者。中位年龄为 69 岁，85.7% 为男性，57.7% 有乙型肝炎感染，60.7% 有 ECOG 0，78.0% 有 Child-Pugh A 肝硬化。82.7% 接受 ICI 单药治疗，17.3% 接受 ICI 联合治疗。irAE的发展和严重程度与生存相关。≥3 级 irAE 与 1-2 级 irAE 与无 irAE 的中位 PFS 分别为 8.5 与 3.6 与 1.3 个月（p #x3c；0.001）。≥3 级 irAE 与 1-2 级 irAE 与无 irAE 的中位 OS 分别为 26.9 与 14.0 与 4.6 个月（p #x3c；0.001）。在多变量分析中，≥2 irAE 的患者 OS 显着延长（调整后的风险比 [aHR]0.35，p#x3c; 0.001)。在 6 周界标（aHR0.34， p = 0.030）和 12 周界标（aHR0.28，p = 0.011）的多变量分析中，≥3 级 irAE 的存在与显着更长的 OS 相关。在 irAE 患者中使用全身性皮质类固醇与延长 OS 的趋势相关（20.7 对 14.3 个月，p = 0.064）。结论：我们的研究表明，全级别 irAE 的存在可能是接受 ICI 治疗的 aHCC 患者的潜在预后生物标志物。具有更严重 irAE 和多系统受累的患者预后更好。迅速使用全身性皮质类固醇治疗 irAE 患者是确保这些患者获得最佳长期结果的关键。
肝癌