Introduction Despite the emergence of atezolizumab and bevacizumab (A + B) as standard first-line systemic therapy for unresectable hepatocellular carcinoma (HCC), a comprehensive understanding of the clinical significance of immune-related adverse events (irAEs) remains limited. We aimed to assess the impact of irAEs on patients with HCC undergoing A + B treatment. Methods This multicentre retrospective study included consecutive patients with HCC who were treated with the A + B regimen from September 2020 to December 2022. Patients were categorized into three groups based on the severity of irAEs, ranging from those without any experience of irAEs to those with severe irAEs. Results This study included 150 patients with HCC, with a mean age of 63.3 years. Among them, 93.3% of patients were classified as Barcelona Clinic Liver Cancer stage C, 52.0% had portal vein tumour thrombosis (PVTT), and 60.7% extrahepatic spread. Patients were classified as follows: group 1 (n = 84) had no irAEs, group 2 (n = 37) had mild irAEs (grade 1-2), and group 3 (n = 29) had severe irAEs (grade ≥3). The median overall survival (OS), progression-free survival (PFS), and time-to-treatment discontinuation (TTD) were 13.6, 5.7, and 3.6 months, respectively. Group 2 demonstrated significantly superior OS compared to group 1 (9.5 months) and group 3 (5.6 months), with a median OS of 23.0 months (p < 0.001). Furthermore, group 2 demonstrated significantly better outcomes in terms of PFS and TTD compared to both group 1 and group 3 (p < 0.001 for both). Multivariate analysis identified mild irAEs (hazard ratio [HR], 0.353; p = 0.010), ALBI grade 1 (HR, 0.389; p = 0.006), Child-Pugh class A (HR, 0.338; p = 0.002), and the absence of PVTT (HR, 0.556; p = 0.043) as independent predictors of better OS. Conclusion Our study highlights the significant impact of irAE severity on the outcomes of patients with HCC receiving A + B. Notably, the occurrence of mild irAEs was independently associated with favourable survival, suggesting their potential role as surrogate indicators of HCC prognosis.

中文翻译：

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阿特朱单抗和贝伐单抗在肝细胞癌患者中的免疫相关不良事件分析：多中心队列研究。


简介 尽管阿特珠单抗和贝伐单抗 (A + B) 已成为不可切除的肝细胞癌 (HCC) 的标准一线全身治疗，但对免疫相关不良事件 (irAE) 临床意义的全面了解仍然有限。我们的目的是评估 irAE 对接受 A + B 治疗的 HCC 患者的影响。方法 这项多中心回顾性研究纳入了 2020 年 9 月至 2022 年 12 月期间接受 A + B 方案治疗的连续 HCC 患者。根据 irAE 的严重程度将患者分为三组，从没有任何 irAE 经历的患者到有过 irAE 经历的患者严重的irAE。结果本研究纳入了 150 名 HCC 患者，平均年龄 63.3 岁。其中，93.3%的患者属于巴塞罗那临床肝癌C期，52.0%有门静脉肿瘤血栓（PVTT），60.7%有肝外扩散。患者分类如下：第1组（n = 84）没有irAE，第2组（n = 37）有轻度irAE（1-2级），第3组（n = 29）有严重irAE（≥3级） 。中位总生存期 (OS)、无进展生存期 (PFS) 和停药时间 (TTD) 分别为 13.6、5.7 和 3.6 个月。与第 1 组（9.5 个月）和第 3 组（5.6 个月）相比，第 2 组的 OS 显着优于第 1 组（9.5 个月），中位 OS 为 23.0 个月（p < 0.001）。此外，与第 1 组和第 3 组相比，第 2 组在 PFS 和 TTD 方面表现出显着更好的结果（两者均 p < 0.001）。多变量分析确定了轻度 irAE（风险比 [HR]，0.353；p = 0.010）、ALBI 1 级（HR，0.389；p = 0.006）、Child-Pugh A 级（HR，0.338；p = 0.002）以及不存在PVTT（HR，0.556；p = 0。043）作为更好 OS 的独立预测因子。结论 我们的研究强调了 irAE 严重程度对接受 A + B 治疗的 HCC 患者预后的显着影响。值得注意的是，轻度 irAE 的发生与良好的生存率独立相关，表明它们作为 HCC 预后替代指标的潜在作用。