Skip to main content
SpringerLink
Log in

Organ-specific response with first-line atezolizumab-bevacizumab versus lenvatinib for patients with advanced hepatocellular carcinoma

  • Original Article
  • Published:
Hepatology International Aims and scope Submit manuscript

Abstract

Background

Immune checkpoint inhibitor (ICI)-based treatments have become the mainstay of first-line treatment for unresectable hepatocellular carcinoma (HCC), but there has been a concern that intrahepatic HCC lesions may be less responsive to ICI monotherapy. We aimed to investigate the organ-specific response patterns among unresectable HCC patients treated with first-line atezolizumab-bevacizumab or lenvatinib.

Methods

This retrospective study included 386 patients with Child–Pugh A unresectable HCC who were treated with first-line atezolizumab-bevacizumab (n = 217) or lenvatinib (n = 169). The organ-specific response was separately evaluated according to the site of the lesions: liver, lung, lymph node (LN), and intraabdomen based on a radiological evaluation adopted from RECIST v 1.1.

Results

The median age was 60 years. Hepatitis B infection was the most common etiology (n = 270, 69.9%), and 291 (75.4%) patients had a viral etiology. The proportion of patients achieving a ≥ 30% reduction in the tumor burden for each organ category was overall higher in the atezolizumab-bevacizumab group than that in the lenvatinib group: 20.2% vs. 11.8%, 23.0% vs. 12.2%, 27.9% vs. 17.9% and 33.3% vs. 15.0% for intrahepatic, lung, LN, and intraabdominal lesions, respectively. The corresponding values for the subgroup with a viral etiology were 17.3% vs. 8.1%, 18.8% vs. 13.3%, 28.9% vs. 3.6%, and 36.0% vs. 12.5%, respectively.

Conclusion

Compared to lenvatinib, atezolizumab-bevacizumab was associated with a favorable organ-specific response regardless of the site of the tumor lesions. Unlike anti-PD-1 monotherapy, atezolizumab-bevacizumab had a comparable organ-specific response between intrahepatic and extrahepatic lesions, especially for those with viral etiology HCCs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Abbreviations

HCC:

Hepatocellular carcinoma

ICI:

Immune checkpoint inhibitor

MKI:

Multikinase inhibitor

OS:

Overall survival

LN:

Lymph node

ECOG:

Eastern Cooperative Oncology Group

ALBI:

Albumin-bilirubin

BCLC:

Barcelona Clinic Liver Cancer

RECIST:

Response Evaluation Criteria in Solid Tumors

PFS:

Progression-free survival

AST:

Aspartate aminotransferase

IQR:

Interquartile range

ORR:

Objective response rate

CI:

Confidence interval

AFP:

Alpha-fetoprotein

References

  1. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–249

    Article  PubMed  Google Scholar 

  2. Vogel A, Meyer T, Sapisochin G, et al. Hepatocellular carcinoma. Lancet. 2022;400:1345–1362

    Article  CAS  PubMed  Google Scholar 

  3. Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382:1894–1905

    Article  CAS  PubMed  Google Scholar 

  4. Abou-Alfa GK, Lau G, Kudo M, Chan SL, Kelley RK, Furuse J, et al. Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. NEJM Evid. 2022;1:8

    Article  Google Scholar 

  5. Qin S, Chan SL, Gu S, et al. Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): a randomised, open-label, international phase 3 study. Lancet. 2023;402:1133–1146

    Article  CAS  PubMed  Google Scholar 

  6. Hegde S, Krisnawan VE, Herzog BH, et al. Dendritic cell paucity leads to dysfunctional immune surveillance in pancreatic cancer. Cancer Cell. 2020;37(289–307): e9

    Google Scholar 

  7. Donne R, Lujambio A. The liver cancer immune microenvironment: Therapeutic implications for hepatocellular carcinoma. Hepatology. 2023;77:1773–1796

    Article  PubMed  Google Scholar 

  8. Yu J, Green MD, Li S, et al. Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination. Nat Med. 2021;27:152–164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Lu LC, Hsu C, Shao YY, et al. Differential organ-specific tumor response to immune checkpoint inhibitors in hepatocellular carcinoma. Liver Cancer. 2019;8:480–490

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kim HS, Kim CG, Hong JY, et al. The presence and size of intrahepatic tumors determine the therapeutic efficacy of nivolumab in advanced hepatocellular carcinoma. Ther Adv Med Oncol. 2022;14:17588359221113266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kudo M, Finn RS, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018;391:1163–1173

    Article  CAS  PubMed  Google Scholar 

  12. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–247

    Article  CAS  PubMed  Google Scholar 

  13. Cheon J, Chon HJ, Bang Y, et al. Real-world efficacy and safety of lenvatinib in Korean patients with advanced hepatocellular carcinoma: a multicenter retrospective analysis. Liver Cancer. 2020;9:613–624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Casadei-Gardini A, Scartozzi M, Tada T, et al. Lenvatinib versus sorafenib in first-line treatment of unresectable hepatocellular carcinoma: an inverse probability of treatment weighting analysis. Liver Int. 2021;41:1389–1397

    Article  CAS  PubMed  Google Scholar 

  15. Kuo YH, Lu SN, Chen YY, et al. Real-world lenvatinib versus sorafenib in patients with advanced hepatocellular carcinoma: a propensity score matching analysis. Front Oncol. 2021;11: 737767

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Xu YJ, Lai ZC, He MK, et al. Toripalimab combined with hepatic arterial infusion chemotherapy versus lenvatinib for advanced hepatocellular carcinoma. Technol Cancer Res Treat. 2021;20:15330338211063848

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Campani C, Vallot A, Ghannouchi H, et al. Impact of radiological response and pattern of progression in patients with hepatocellular carcinoma treated by atezolizumab- bevacizumab. Hepatology. 2023. https://doi.org/10.1016/S0168-8278(23)01389-2

    Article  PubMed  Google Scholar 

  18. Yang J, Yan J, Liu B. Targeting VEGF/VEGFR to modulate antitumor immunity. Front Immunol. 2018;9:978

    Article  PubMed  PubMed Central  Google Scholar 

  19. Zhang Y, Huang H, Coleman M, et al. VEGFR2 activity on myeloid cells mediates immune suppression in the tumor microenvironment. JCI Insight. 2021. https://doi.org/10.1172/jci.insight.150735

    Article  PubMed  PubMed Central  Google Scholar 

  20. Wu C, Lin J, Weng Y, et al. Myeloid signature reveals immune contexture and predicts the prognosis of hepatocellular carcinoma. J Clin Invest. 2020;130:4679–4693

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Zhu AX, Abbas AR, de Galarreta MR, et al. Molecular correlates of clinical response and resistance to atezolizumab in combination with bevacizumab in advanced hepatocellular carcinoma. Nat Med. 2022;28:1599–1611

    Article  CAS  PubMed  Google Scholar 

  22. Yukami H, Kawazoe A, Lin YT, et al. Updated efficacy outcomes of anti-PD-1 antibodies plus multikinase inhibitors for patients with advanced gastric cancer with or without liver metastases in clinical trials. Clin Cancer Res. 2022;28:3480–3488

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Pfister D, Nunez NG, Pinyol R, et al. NASH limits anti-tumour surveillance in immunotherapy-treated HCC. Nature. 2021;592:450–456

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Casadei-Gardini A, Rimini M, Tada T, et al. Atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a large real-life worldwide population. Eur J Cancer. 2023;180:9–20

    Article  CAS  PubMed  Google Scholar 

  25. Espinoza M, Muquith M, Lim M, et al. Disease etiology and outcomes after atezolizumab plus bevacizumab in hepatocellular carcinoma: post-hoc analysis of IMbrave150. Gastroenterology. 2023;165:286–8.e4

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

No funding was received for this study.

Author information

Author notes

  1. Hyung-Don Kim and Young-Gyu Park equally contributed to this work and shared as co-first authors.

Authors and Affiliations

  1. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea

    Hyung-Don Kim, Young-Gyu Park, Sejin Kim, Kyu-Pyo Kim, Sook-Ryun Park, Min-Hee Ryu, Baek-Yeol Ryoo & Changhoon Yoo

Authors
  1. Hyung-Don Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Young-Gyu Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sejin Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kyu-Pyo Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sook-Ryun Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Min-Hee Ryu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Baek-Yeol Ryoo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Changhoon Yoo
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Study concepts: HDK and CY; study design: HDK and CY; data acquisition: HDK, YGP, SK, KPK, SRP, MHR, BYR, and CY; data analysis and interpretation: HDK, YGP, and CY; statistical analysis: HDK and YGP; manuscript preparation: HDK and YGP; manuscript editing: HDK, YGP, and CY; manuscript review and approval: HDK, YGP, SK, KPK, SRP, MHR, BYR, and CY.

Corresponding author

Correspondence to Changhoon Yoo.

Ethics declarations

Conflict of interest

CY received honoraria from Servier, Bayer, AstraZeneca, Merck Sharp & Dohme, Eisai, Celgene, Bristol Myers Squibb, Ipsen, Novartis, Boryung Pharmaceuticals, Mundipharma, and Roche, and received research grants from Servier, Bayer, AstraZeneca, Ono Pharmaceuticals, Ipsen, and Boryung Pharmaceuticals. HDK received honoraria from AstraZeneca, Bristol Myers Squibb, Ono Pharmaceuticals, Boryung Pharmaceuticals, and Boostimmune. The other authors have nothing to disclose.

Ethical approval and informed consent

This study was approved by the Institutional Review Board of Asan Medical Center (IRB No. 2021-0064) and was performed in accordance with the ethical standards of the Institutional Research Committee and the latest Declaration of Helsinki. The need for informed consent was waived by the Institutional Review Board of Asan Medical Center.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 1310 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, HD., Park, YG., Kim, S. et al. Organ-specific response with first-line atezolizumab-bevacizumab versus lenvatinib for patients with advanced hepatocellular carcinoma. Hepatol Int (2024). https://doi.org/10.1007/s12072-023-10626-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12072-023-10626-6

Keywords

Search

Navigation