Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Oct;56(4):1231-1239.
doi: 10.4143/crt.2024.237. Epub 2024 May 27.

Distinct Characteristics and Changes in Liver Function of Patients with Hepatocellular Carcinoma Treated with Atezolizumab Plus Bevacizumab for More Than 1 Year

Youngun Kim  1 , Jung Sun Kim  2 , Beodeul Kang  1   2 , Ilhwan Kim  3 , Hyeyeong Kim  4 , Won Suk Lee  2 , Yun Beom Sang  1   2 , Sanghoon Jung  5 , Chansik An  5 , Chan Kim  1   2 , Hong Jae Chon  1   2
Affiliations

Distinct Characteristics and Changes in Liver Function of Patients with Hepatocellular Carcinoma Treated with Atezolizumab Plus Bevacizumab for More Than 1 Year

Youngun Kim et al. Cancer Res Treat. 2024 Oct.

Abstract

Purpose: Since 2020, atezolizumab plus bevacizumab (Ate/Bev) has been the standard first-line therapy for unresectable hepatocellular carcinoma (HCC), but long-term treatment studies are limited. This study evaluated the clinical characteristics and effects of Ate/Bev for over 1 year.

Materials and methods: This study included patients with unresectable HCC treated with first-line Ate/Bev between May 2020 and April 2022. Those receiving Ate/Bev for 1 year or more were classified as the long-term treatment group.

Results: Of 246 patients, 69 (28.0%) were in the long-term treatment group, which comprised more proportions of intrahepatic tumor burden < 25%, Eastern Cooperative Oncology Group 0, and a lower proportion of portal vein tumor thrombosis than the short-term treatment group. The long-term treatment group had a higher incidence of atezolizumab-related thyroid dysfunction (31.9% vs. 10.7%, p < 0.001; median time to onset [mTTO], 2.8 months), dermatologic toxicity (29.0% vs. 14.7%, p=0.017; mTTO, 3.3 months), bevacizumab-related hypertension (44.9% vs. 22.0%, p=0.001; mTTO, 4.2 months), and proteinuria (69.6% vs. 38.4%, p < 0.001; mTTO, 6.8 months), compared to the short-term treatment group. Regarding liver function in the long-term treatment group, patients initially classified as Child-Pugh class A decreased from 87.0% to 75.4%, and albumin-bilirubin grade 1 decreased from 68.1% to 50.7% after 1 year of treatment.

Conclusion: The Ate/Bev long-term treatment group had a lower intrahepatic tumor burden, less portal vein tumor thrombosis, and better performance status and liver function at baseline. Atezolizumab-related immunological adverse events emerged relatively early in treatment compared to the bevacizumab-related. Additionally, some patients demonstrated liver function deterioration during long-term Ate/Bev treatment.

Keywords: Atezolizumab; Bevacizumab; Hepatocellular carcinoma; Immune checkpoint inhibitor; Intrahepatic tumor burden; Therapeutics; Unresectable.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest

Hong Jae Chon has consulting or advisory roles at Eisai, Roche, Bayer, ONO, MSD, BMS, Celgene, Sanofi, Servier, AstraZeneca, SillaJen, Menarini, and GreenCross Cell, and has received research grants from Roche, Dong-A ST, and Boryung Pharmaceuticals. Chan Kim has consulting or advisory roles at Roche, ONO, MSD, BMS, Oncocross, and Virocure, and has received research grants from Boryung Pharmaceuticals, Oncocross, SillaJen, and Virocure.

Figures

Fig. 1.
Fig. 1.
Survival outcomes according to the intrahepatic tumor burden: PFS (A), OS (B), objec tive response rate (C). CI, confidence interval; CR, complete response; NR, not reached; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease.
Fig. 2.
Fig. 2.
Changes in liver function over 12 months of atezolizumab plus bevacizumab treatment in the long-term treatment group (n=69). (A) Child-Pugh (CP) score. (B) Albumin-Bilirubin grade.
Fig. 3.
Fig. 3.
Proportions of patients maintained on atezolizumab plus bevacizumab treatment over two years (separate cohort).
See this image and copyright information in PMC

References

    1. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–90. - PubMed
    1. Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018;391:1163–73. - PubMed
    1. Llovet JM, Pinyol R, Kelley RK, El-Khoueiry A, Reeves HL, Wang XW, et al. Molecular pathogenesis and systemic therapies for hepatocellular carcinoma. Nat Cancer. 2022;3:386–401. - PMC - PubMed
    1. Yang C, Zhang H, Zhang L, Zhu AX, Bernards R, Qin W, et al. Evolving therapeutic landscape of advanced hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2023;20:203–22. - PubMed
    1. Llovet JM, Hernandez-Gea V. Hepatocellular carcinoma: reasons for phase III failure and novel perspectives on trial design. Clin Cancer Res. 2014;20:2072–9. - PubMed

MeSH terms