Skip to main content

Advertisement

Log in

Efficacy of apatinib in patients with sorafenib–transarterial chemoembolization refractory hepatocellular carcinoma: a retrospective study

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

Abstract

Purpose

To investigate the efficacy of sequential apatinib treatment in patients with unresectable hepatocellular carcinoma (HCC) refractory to sorafenib–transarterial chemoembolization (TACE).

Materials and methods

This respective study was conducted on 95 consecutive patients with sorafenib–TACE-refractory unresectable HCC in our center from January 2014 to December 2019. According to the response to sorafenib–TACE treatment and the subsequent management, the eligible patients were assigned into three groups: sorafenib–TACE (ST) group, sorafenib–TACE–apatinib (STA) group, and sorafenib–TACE–supportive care (STS) group. The differences in overall survival (OS) and tumor response were compared among the three groups. Risk factors related to prognosis were analyzed.

Results

A total of 58 patients were enrolled in the study, with 11, 15, and 28 patients in ST, STA, and STS group, respectively. The median OS of the STA group was significantly improved when compared with the STS group, either from the start of sorafenib–TACE resistance or the initiation of sorafenib–TACE therapy (14.0 versus 4.0 months, p = 0.003; 19.0 versus 9.0 months, p < 0.001; respectively). Additionally, from the start of sorafenib–TACE treatment, the median OS of the STA group was longer than that of the ST group without statistical difference (19.0 versus 15.0 months, p = 0.28), so did the comparison of median OS between the ST group and the STS group (15.0 versus 9.0 months, p = 0.06). Extrahepatic metastases were an independent risk factor for poor prognosis.

Conclusion

In patients with sorafenib–TACE-refractory HCC, subsequent apatinib treatment significantly improved the OS when compared with supportive care, and produced comparative outcomes with those sorafenib–TACE responders.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

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. 2020. https://doi.org/10.3322/caac.21660.

  2. Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020–2.

    Article  Google Scholar 

  3. European Association for the Study of the Liver, European Organisation for Research and Treatment of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012; 56: 908–43.

  4. Cheng A-L, Kang Y-K, Chen Z, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10:25–34.

    Article  CAS  Google Scholar 

  5. Llovet JM, Ricci S, Mazzaferro V, Hilgard P. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–90.

    Article  CAS  Google Scholar 

  6. Abou-Alfa GK, Meyer T, Cheng AL, et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med. 2018;379:54–63.

    Article  CAS  Google Scholar 

  7. Bruix J, Qin S, Merle P, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;389:56–66.

    Article  CAS  Google Scholar 

  8. Zhu AX, Park JO, Ryoo B-Y, et al. Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2015;16:859–70.

    Article  CAS  Google Scholar 

  9. Tian S, Quan H, Xie C, et al. YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with potent activity in vitro and in vivo. Cancer Sci. 2011;102:1374–80.

    Article  CAS  Google Scholar 

  10. Qin S. Apatinib in Chinese patients with advanced hepatocellular carcinoma: a phase II randomized, open-label trial. J Clin Oncol. 2014;32:4019–4019.

    Article  Google Scholar 

  11. Zhen L, Jiali C, Yong F, et al. The efficacy and safety of apatinib treatment for patients with unresectable or relapsed liver cancer: a retrospective study. J Cancer. 2018;9:2773–7.

    Article  Google Scholar 

  12. Kan X, Liang B, Zhou G, et al. Transarterial chemoembolization combined with apatinib for advanced hepatocellular carcinoma: a propensity score matching analysis. Front Oncol. 2020;10:970.

    Article  Google Scholar 

  13. Zhang Y, Huang G, Miao H, et al. Apatinib treatment may improve survival outcomes of patients with hepatitis B virus-related sorafenib-resistant hepatocellular carcinoma. Ther Adv Med Oncol. 2020;12:1758835920937422.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Kudo M, Ueshima K, Ikeda M, et al. Randomised, multicentre prospective trial of transarterial chemoembolisation (TACE) plus sorafenib as compared with TACE alone in patients with hepatocellular carcinoma: TACTICS trial. Gut. 2020;69:1492–501.

    Article  Google Scholar 

  15. Zhang Y, Fan W, Wang Y, et al. Apatinib for Patients with sorafenib-refractory advanced hepatitis B virus related hepatocellular carcinoma: results of a pilot study. Cancer Control. 2019;26:1073274819872216.

    Article  Google Scholar 

  16. Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010;30:52–60.

    Article  CAS  Google Scholar 

  17. Kudo M, Matsui O, Izumi N, et al. Transarterial chemoembolization failure/refractoriness: JSH-LCSGJ criteria 2014 update. Oncology. 2014;87(Suppl 1):22–31.

    Article  CAS  Google Scholar 

  18. Palmer DH. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:2498; author reply 2498–9.

  19. Kim HY, Park JW, Joo J, et al. Severity and timing of progression predict refractoriness to transarterial chemoembolization in hepatocellular carcinoma. J Gastroenterol Hepatol. 2012;27:1051–6.

    Article  Google Scholar 

  20. Arizumi T, Minami T, Chishina H, et al. Time to Transcatheter arterial chemoembolization refractoriness in patients with hepatocellular carcinoma in kinki criteria stages B1 and B2. Dig Dis. 2017;35:589–97.

    Article  Google Scholar 

  21. Liu KC, Hao YH, Lv WF, et al. Transarterial Chemoembolization combined with sorafenib in patients with BCLC stage C hepatocellular carcinoma. Drug Des Dev Ther. 2020;14:3461–8.

    Article  CAS  Google Scholar 

  22. Yuan J, Yin X, Tang B, et al. Transarterial chemoembolization (TACE) combined with sorafenib in treatment of HBV background hepatocellular carcinoma with portal vein tumor thrombus: a propensity score matching study. Biomed Res Int. 2019;2019:2141859.

    PubMed  PubMed Central  Google Scholar 

  23. Finn RS, Merle P, Granito A, et al. Outcomes of sequential treatment with sorafenib followed by regorafenib for HCC: additional analyses from the phase III RESORCE trial. J Hepatol. 2018;69:353–8.

    Article  CAS  Google Scholar 

  24. Liu K, Min XL, Peng J, et al. The changes of HIF-1alpha and VEGF expression after TACE in patients with hepatocellular carcinoma. J Clin Med Res. 2016;8:297–302.

    Article  CAS  Google Scholar 

  25. Shim JH, Park J-W, Kim JH, et al. Association between increment of serum VEGF level and prognosis after transcatheter arterial chemoembolization in hepatocellular carcinoma patients. Cancer Sci. 2008;99:2037–44.

    CAS  PubMed  Google Scholar 

  26. Niu L, Liu L, Yang S, et al. New insights into sorafenib resistance in hepatocellular carcinoma: responsible mechanisms and promising strategies. Biochim Biophys Acta Rev Cancer. 2017;1868:564–70.

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by a grant from the National Natural Science Foundation of China (No. 81873919).

Author information

Authors and Affiliations

Authors

Contributions

Chuansheng Zheng conceived and designed the study. Yanyan Cao contributed significantly to analysis and manuscript preparation. Tao Ouyang performed the data analysis and wrote the manuscript. Fu Xiong, Xuefeng Kan, Lei Chen, and Bin Liang helped to perform the analysis with constructive discussions. All authors read and approved the manuscript.

Corresponding author

Correspondence to Chuansheng Zheng.

Ethics declarations

Conflict of interest

The study was conducted according to the Declaration of Helsinki. Informed consent was waived for the retrospective type of this study. The information of all participants is maintained with confidentiality. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Consent to participates

All patients were informed that apatinib was an alternative treatment, because the first-line sorafenib–TACE treatment was ineffective. Moreover, all patients were informed of the economic cost, anticipated outcomes, and potential toxicity. Final treatment decisions were made by the patients.

Additional information

Publisher's Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cao, Y., Ouyang, T., Xiong, F. et al. Efficacy of apatinib in patients with sorafenib–transarterial chemoembolization refractory hepatocellular carcinoma: a retrospective study. Hepatol Int 15, 1268–1277 (2021). https://doi.org/10.1007/s12072-021-10198-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12072-021-10198-3

Keywords

Navigation