Analysis of Immune-Related Adverse Events of Atezolizumab and Bevacizumab in Patients with Hepatocellular Carcinoma: A Multicenter Cohort Study

IF 11.6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Liver Cancer Pub Date : 2023-12-21 DOI:10.1159/000535839
H. Nam, Jaejun Lee, J. Han, S. Lee, Hyun Yang, H. Lee, P. Sung, H. Kim, Seok-Hwan Kim, Myeong Jun Song, J. Kwon, Chang Wook Kim, S. Nam, Si Hyun Bae, J. Choi, S. Yoon, J. W. Jang
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Abstract

Background: 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 categorised into three groups based on the severity of irAEs, ranging from those without any experience of irAEs to those with severe irAEs, classified as grade 3 or higher. 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. Conclusions: 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.
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肝细胞癌患者使用阿妥珠单抗和贝伐珠单抗的免疫相关不良事件分析:一项多中心队列研究
背景:尽管阿特珠单抗和贝伐单抗(A+B)已成为不可切除肝细胞癌(HCC)的标准一线系统疗法,但对免疫相关不良事件(irAEs)临床意义的全面了解仍然有限。我们旨在评估irAEs对接受A+B治疗的HCC患者的影响: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irAEs的严重程度将患者分为三组,从没有任何irAEs经历的患者到有严重irAEs(分为3级或以上)的患者:本研究共纳入 150 名 HCC 患者,平均年龄为 63.3 岁。其中,93.3%的患者属于巴塞罗那临床肝癌C期,52.0%的患者有门静脉瘤栓形成(PVTT),60.7%的患者有肝外扩散。患者分类如下第1组(84人)无虹膜不良反应,第2组(37人)有轻度虹膜不良反应(1-2级),第3组(29人)有重度虹膜不良反应(≥3级)。中位总生存期(OS)、无进展生存期(PFS)和终止治疗时间(TTD)分别为13.6个月、5.7个月和3.6个月。第2组的OS明显优于第1组(9.5个月)和第3组(5.6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 方面的疗效明显更好(均 p <0.001)。多变量分析发现,轻度irAEs(危险比[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)和无PVTT(HR,0.556;p = 0.043)是较好OS的独立预测因素:我们的研究强调了irAE严重程度对接受A+B治疗的HCC患者预后的重要影响。结论:我们的研究强调了irAE严重程度对接受A+B治疗的HCC患者预后的重要影响,值得注意的是,轻度irAE的发生与良好的生存率独立相关,这表明轻度irAE可能成为HCC预后的替代指标。
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来源期刊
Liver Cancer
Liver Cancer Medicine-Oncology
CiteScore
20.80
自引率
7.20%
发文量
53
审稿时长
16 weeks
期刊介绍: Liver Cancer is a journal that serves the international community of researchers and clinicians by providing a platform for research results related to the causes, mechanisms, and therapy of liver cancer. It focuses on molecular carcinogenesis, prevention, surveillance, diagnosis, and treatment, including molecular targeted therapy. The journal publishes clinical and translational research in the field of liver cancer in both humans and experimental models. It publishes original and review articles and has an Impact Factor of 13.8. The journal is indexed and abstracted in various platforms including PubMed, PubMed Central, Web of Science, Science Citation Index, Science Citation Index Expanded, Google Scholar, DOAJ, Chemical Abstracts Service, Scopus, Embase, Pathway Studio, and WorldCat.
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