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
{"title":"Analysis of Immune-Related Adverse Events of Atezolizumab and Bevacizumab in Patients with Hepatocellular Carcinoma: A Multicenter Cohort Study","authors":"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","doi":"10.1159/000535839","DOIUrl":null,"url":null,"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.\nMethods: 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.\nResults: 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.\nConclusions: 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.\n","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":null,"pages":null},"PeriodicalIF":11.6000,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Liver Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000535839","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0
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.
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.