Sorafenib for advanced hepatocellular carcinoma provides better prognosis after liver transplantation than without liver transplantation

Abstract

Background

Although sorafenib has been used to treat advanced hepatocellular carcinoma (HCC), the efficacy of sorafenib in patients with recurrent HCCs after liver transplantation (LT) has not been compared with that in patients without LT (non-LT).

Methods

Between 2008 and 2019, a total of 832 consecutive HCC patients treated with sorafenib (790 in the non-LT group and 42 in the LT group) were enrolled. The primary outcome was overall survival (OS). Secondary outcomes were time-to-progression (TTP), objective response rate (ORR) and disease control rate (DCR). Treatment outcomes were assessed by multiple subgroup analyses and propensity-score matching (PSM).

Results

The median follow-up duration was 152.5 days. The LT group was younger and had smaller intrahepatic HCC than the non-LT group. The LT group showed significantly better OS (16.8 vs. 7.1 months, p < 0.001), TTP, ORR and DCR than the non-LT group. The superior efficacy of sorafenib in the LT group was corroborated in multiple subgroup analyses stratified by metastasis, effective sorafenib maintenance dose, or Child-Turcotte-Pugh class A. LT was identified as an independent factor for favorable OS. Intrahepatic HCC was the strongest tumor-related factor for both OS and TTP and was significantly associated with tumor response and hepatic function. Finally, subanalyses including only patients with small intrahepatic HCC or PSM modeling showed no difference in sorafenib efficacy between the LT and the non-LT groups.

Conclusion

Sorafenib provides better outcomes in the LT setting than the non-LT setting. This benefit may be associated with the smaller intrahepatic HCC coupled with preserved hepatic function in LT recipients.

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Data availability

The data that support the findings of this study are available from the corresponding author, upon reasonable request.

Abbreviations

HCC:

Hepatocellular carcinoma

LT:

Liver transplantation

CTP:

Child-Turcotte-Pugh

CT:

Computed tomography

MRI:

Magnetic resonance imaging

BCLC:

Barcelona clinic liver cancer

mUICC:

Modified union for international cancer control

OS:

Overall survival

TTP:

Time to progression

ORR:

Objective response rate

DCR:

Disease control rate

mRECIST:

Modified response evaluation criteria in solid tumor

SD:

Standard deviation

PSM:

Propensity-score matching

AFP:

Alpha fetoprotein

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Funding

This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2019R1A2C1009439).

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Authors

Contributions

Study concept and design: JJW. Acquisition of data: KHY, SDS, KCW, SMJ, CHJ, YYK, BSH, YSK. Analysis and interpretation of data: LSK, NH, SPS, LSW, KJH, CJY. Drafting of the manuscript: LSK. Study supervision: JJW.

Corresponding author

Correspondence to Jeong Won Jang.

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Conflicts of interest

The authors have no financial or personal relationships with other persons or organizations that could inappropriately affect the work. Jeong Won Jang has served as a consultant to or has served on the advisory board of BMS, Gilead, AbbVie, and Bayer. Soon Kyu Lee, Jeong Won Jang, Heechul Nam, Pil Soo Sung, Hee Yeon Kim, Jung Hyun Kwon, Sung Won Lee, Do Seon Song, Chang Wook Kim, Myeong Jun Song, Ho Joong Choi, Young Kyoung You, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon have no conflicts of interests.

Ethics approval

This study was approved by the Institutional Review Board of the Catholic University of Korea (XC20RIDI0073).

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Informed consents were waived by the Institutional Reviewer Board of Catholic University of Korea due to retrospective design of the study.

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Lee, S.K., Jang, J.W., Nam, H. et al. Sorafenib for advanced hepatocellular carcinoma provides better prognosis after liver transplantation than without liver transplantation. Hepatol Int 15, 137–145 (2021). https://doi.org/10.1007/s12072-020-10131-0

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Keywords

  • Sorafenib
  • Liver transplantation
  • Hepatocellular carcinoma
  • Liver function
  • Tumor size