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Letter to the Editor

Letter to the editor on “Sorafenib vs. Lenvatinib in advanced hepatocellular carcinoma after atezolizumab/bevacizumab failure: A real-world study”

Meng-Che Wu1,2,3, Hui-Chin Chang3,4,5, Yi-Sheng Jhang6orcid, Shuo-Yan Gau7,8,9
Clinical and Molecular Hepatology 2025;31(1):e13-e14.
Published online: September 2, 2024

1Division of Pediatric Gastroenterology, Children’s Medical Center, Taichung Veterans General Hospital, Taichung, Taiwan

2Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan

3School of Medicine, Chung Shan Medical University, Taichung, Taiwan

4Evidence-based Medicine Center, Chung Shan Medical University Hospital, Taichung, Taiwan

5Library, Chung Shan Medical University Hospital, Taichung, Taiwan

6Department of Pharmacy, Chung Shan Medical University Hospital, Taichung, Taiwan

7Department and Graduate Institute of Business Administration, National Taiwan University, Taipei, Taiwan

8Department of Pharmacology, Chung Shan Medical University, Taichung, Taiwan

9Orthopedics Department, Chi-Mei Medical Center, Tainan, Taiwan

Corresponding author : Yi-Sheng Jhang Department of Pharmacy, Chung Shan Medical University Hospital, No. 110, Sec. 1, Jianguo N. Rd., South District, Taichung City 40201, Taiwan Tel: +886-4-24739595, Fax: +886-4-24728907, E-mail: vp45jknck5s@gmail.com

Editor: Gi-Ae Kim, Kyung Hee University, Korea

• Received: August 18, 2024   • Revised: August 29, 2024   • Accepted: August 30, 2024

Copyright © 2025 by The Korean Association for the Study of the Liver

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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See the reply "Correspondence to letter to the editor on “Sorafenib vs. lenvatinib in advanced hepatocellular carcinoma after atezolizumab/bevacizumab failure: a real-world study”" in Volume 31 on page e98.
See the article "Sorafenib vs. Lenvatinib in advanced hepatocellular carcinoma after atezolizumab/bevacizumab failure: A real-world study" on page 345.
  • Keywords: Hepatocellular carcinoma; Cohort study; Epidemiology
    • Dear Editor,
    The real-world study by Chon et al., titled “Sorafenib vs. Lenvatinib in advanced hepatocellular carcinoma after atezolizumab/bevacizumab failure: A real-world study,” highlights important observations on the differences between second-line treatments for advanced hepatocellular carcinoma (HCC) after first-line treatment with atezolizumab plus bevacizumab (ATE+BEV [1]. Although the study is important, certain issues could be addressed in future studies to improve the accuracy and applicability of the results in clinical practice.
    Firstly, the impact of specific tumor characteristics, such as macrovascular invasion and extrahepatic metastasis, on treatment outcomes could be explored in more depth. These parameters have a clear impact on the prognosis of advanced HCC. For instance, previous trials have reported that the grade of macrovascular invasion is a complex parameter, which on one hand offers a poorer prognosis and potentially affects systemic therapies like tyrosine kinase inhibitors (TKIs) such as sorafenib and lenvatinib [2]. Patient stratification by these characteristics may offer a personalized method to identify subgroups more likely to benefit from lenvatinib compared with sorafenib.
    The second issue concerns the propensity score matching process. Propensity score matching is widely utilized in real-world study designs [3]. Although the authors attempted to adjust for baseline characteristics (i.e., patients with comparable treatment histories) using propensity score matching, a significant difference remained in the number of cycles the two groups received before ATE/BEV after matching (P=0.007, as indicated in Table 1 of the Chon et al. study1). The number of cycles could impact subsequent therapy due to the development of upfront resistance mechanisms [4]. A deeper exploration of the impact of preceding ATE+BEV exposure on second-line therapy response would better inform these findings.
    Finally, the study suggests that larger and possibly longer-term studies are needed, with a focus on how lenvatinib or sorafenib should be chosen based on tumor molecular profiling, if any. Current evidence suggests that molecular profiling may even differentiate those patients with HCC who will benefit from TKIs [5]. Identifying these detectable predictive markers could eventually allow future studies to be more targeted, resulting in more desirable outcomes for patients.
    In conclusion, Chon et al.’s study offers valuable insights into second-line treatments for advanced HCC but would benefit from further exploration of tumor characteristics, refined propensity score matching, and the potential of molecular profiling. These improvements could enhance the clinical applicability and personalization of treatment strategies.

    Authors’ contribution

    All the authors involved in drafting or revising the article and approved of the submitted version. Study conception and design: Gau SY, Wu MC, Chang HC, Jhang YS. Original draft preparation: Gau SY, Wu MC, Chang HC, Jhang YS.

    Conflicts of Interest

    The authors have no conflicts to disclose.

    ATE+BEV

    atezolizumab plus bevacizumab

    HCC

    hepatocellular carcinoma

    TKIs

    tyrosine kinase inhibitors
    • 1. Chon YE, Kim DY, Kim MN, Kim BK, Kim SU, Park JY, et al. Sorafenib vs. Lenvatinib in advanced hepatocellular carcinoma after atezolizumab/bevacizumab failure: A real-world study. Clin Mol Hepatol 2024;30:345-359.
    • 2. 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;391:1163-1173.
    • 3. Li CP, Lo SW, Tsai RY, Chang HC, Gau SY. New-onset hidradenitis suppurativa in psoriasis patients: A multi-center, retrospective cohort study. Life (Basel) 2024;14:730.
    • 4. Yau T, Park JW, Finn RS, Cheng AL, Mathurin P, Edeline J, et al. CheckMate 459: A randomized, multi-center phase III study of nivolumab (NIVO) vs sorafenib (SOR) as first-line (1L) treatment in patients (pts) with advanced hepatocellular carcinoma (aHCC). Annals of Oncology 2019;30:v874-v875.
    • 5. Peng X, Gong C, Zhang W, Zhou A. Advanced development of biomarkers for immunotherapy in hepatocellular carcinoma. Front Oncol 2023;12:1091088.

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    Letter to the editor on “Sorafenib vs. Lenvatinib in advanced hepatocellular carcinoma after atezolizumab/bevacizumab failure: A real-world study”
    Clin Mol Hepatol. 2025;31(1):e13-e14.   Published online September 2, 2024
    DOI: https://doi.org/10.3350/cmh.2024.0682
    Download Citation

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    Letter to the editor on “Sorafenib vs. Lenvatinib in advanced hepatocellular carcinoma after atezolizumab/bevacizumab failure: A real-world study”
    Clin Mol Hepatol. 2025;31(1):e13-e14.   Published online September 2, 2024
    DOI: https://doi.org/10.3350/cmh.2024.0682
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