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Investigational New Drugs

, Volume 36, Issue 2, pp 332–339 | Cite as

Characteristics of patients with sorafenib-treated advanced hepatocellular carcinoma eligible for second-line treatment

  • Sadahisa Ogasawara
  • Tetsuhiro Chiba
  • Yoshihiko Ooka
  • Eiichiro Suzuki
  • Takahiro Maeda
  • Masayuki Yokoyama
  • Toru Wakamatsu
  • Masanori Inoue
  • Tomoko Saito
  • Kazufumi Kobayashi
  • Soichiro Kiyono
  • Masato Nakamura
  • Shingo Nakamoto
  • Shin Yasui
  • Akinobu Tawada
  • Makoto Arai
  • Tatsuo Kanda
  • Hitoshi Maruyama
  • Osamu Yokosuka
  • Naoya Kato
SHORT REPORT

Summary

Background Regorafenib has been investigated for its efficacy and safety as a second-line treatment in patients with advanced hepatocellular carcinoma (HCC). We assessed the characteristics of patients with HCC treated with sorafenib who might be eligible for second-line treatment in general and regorafenib in particular. Methods Patients with HCC treated with sorafenib were retrospectively analyzed. We defined second-line candidate patients as maintaining Child–Pugh A and ECOG-PS ≤1 at the time of sorafenib failure. We also defined regorafenib candidate patients as follows: 1) continuing sorafenib at the time of radiological progression, 2) maintaining Child–Pugh A and ECOG-PS ≤ 1 at the time of sorafenib failure, and 3) continuing sorafenib 400 mg or more without intolerable adverse events at least 20 days of the last 28 days of treatment. Results Of 185 patients, 130 (70%) and 69 (37%) were candidates for second-line treatment and regorafenib. Child-Pugh score 6 and ECOG-PS 1 at the time of starting sorafenib were significantly lower in both second-line treatment and regorafenib candidate patients. Moreover, hand–foot skin reaction and liver failure during sorafenib treatment were associated with significantly low and high probabilities, respectively, of both Child–Pugh score > 6 and ECOG-PS > 1 at the time of sorafenib failure. Conclusion Regorafenib candidate patients after sorafenib failure are limited, and generally fewer than those who are candidates for second-line treatment. A lower Child–Pugh score and a better ECOG-PS were predictors of eligibility for second-line therapy and regorafenib treatment in sorafenib-treated patients with advanced HCC patients.

Keywords

Hepatocellular carcinoma Sorafenib Second-line Regorafenib Resorce 

Notes

Funding

This research was partially supported by grants from the Japan Society for the Promotion of Science (JSPS) and the Research Program on Hepatitis from Japan Agency for Medical Research and Development (AMED).

Compliance with ethical standards

Conflicts of interest disclosure

Osamu Yokosuka received grant support and honoraria from Bayer. Sadahisa Ogasawara received advisory fee and honoraria from Bayer. The other authors who took part in this study indicated that they did not have anything to declare regarding funding or conflict of interest with respect to this study.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

For this type of study, formal consent was not required.

References

  1. 1.
    Wilhelm SM, Carter C, Tang L et al (2004) BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 64:7099–7109CrossRefPubMedGoogle Scholar
  2. 2.
    Llovet JM, Ricci S, Mazzaferro V et al (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359:378–390CrossRefPubMedGoogle Scholar
  3. 3.
    Cheng AL, Kang YK, Chen Z et al (2009) 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 10:25–34CrossRefPubMedGoogle Scholar
  4. 4.
    Bruix J, Sherman M (2011) American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology 53:1020–1022CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    European Association For The Study Of The Liver; European Organisation For Research And Treatment Of Cancer (2012) EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 56:908–943CrossRefGoogle Scholar
  6. 6.
    Kudo M, Matsui O, Izumi N et al (2014) JSH Consensus-Based Clinical Practice Guidelines for the Management of Hepatocellular Carcinoma: 2014 Update by the Liver Cancer Study Group of Japan. Liver Cancer 3:458–468CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Omata M, Cheng AL, Kokudo N et al (2017) Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int 11:317–370CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Ogasawara S, Chiba T, Ooka Y et al (2014) Efficacy of sorafenib in intermediate-stage hepatocellular carcinoma patients refractory to transarterial chemoembolization. Oncology 87:330–341CrossRefPubMedGoogle Scholar
  9. 9.
    Arizumi T, Ueshima K, Minami T et al (2015) Effectiveness of Sorafenib in Patients with Transcatheter Arterial Chemoembolization (TACE) Refractory and Intermediate-Stage Hepatocellular Carcinoma. Liver Cancer 4:253–262CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Kudo M, Lencioni R, Marrero JA et al (2016) Regional differences in sorafenib-treated patients with hepatocellular carcinoma: GIDEON observational study. Liver Int 36:1196–1205CrossRefPubMedGoogle Scholar
  11. 11.
    Ogasawara S, Chiba T, Ooka Y et al (2016) Analysis of Sorafenib Outcome: Focusing on the Clinical Course in Patients with Hepatocellular Carcinoma. PLoS One 11:e0161303CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Hatooka M, Kawaoka T, Aikata H et al (2016) Comparison of Outcome of Hepatic Arterial Infusion Chemotherapy and Sorafenib in Patients with Hepatocellular Carcinoma Refractory to Transcatheter Arterial Chemoembolization. Anticancer Res 36:3523–3529PubMedGoogle Scholar
  13. 13.
    Llovet JM, Decaens T, Raoul JL et al (2013) Brivanib in patients with advanced hepatocellular carcinoma who were intolerant to sorafenib or for whom sorafenib failed: results from the randomized phase III BRISK-PS study. J Clin Oncol 31:3509–3516CrossRefPubMedGoogle Scholar
  14. 14.
    Zhu AX, Park JO, Ryoo BY et al (2015) 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 16:859–870CrossRefPubMedGoogle Scholar
  15. 15.
    Zhu AX, Kudo M, Assenat E et al (2014) Effect of everolimus on survival in advanced hepatocellular carcinoma after failure of sorafenib: the EVOLVE-1 randomized clinical trial. JAMA 312:57–67CrossRefPubMedGoogle Scholar
  16. 16.
    Kudo M, Moriguchi M, Numata K et al (2017) S-1 versus placebo in patients with sorafenib-refractory advanced hepatocellular carcinoma (S-CUBE): a randomised, double-blind, multicentre, phase 3 trial. Lancet Gastroenterol Hepatol 2:407–417CrossRefPubMedGoogle Scholar
  17. 17.
    Wilhelm SM, Dumas J, Adnane L et al (2011) Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer 129:245–255CrossRefPubMedGoogle Scholar
  18. 18.
    Grothey A, Van Cutsem E, Sobrero A et al (2013) Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 381:303–312CrossRefPubMedGoogle Scholar
  19. 19.
    Demetri GD, Reichardt P, Kang YK et al (2013) Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 381:295–302CrossRefPubMedGoogle Scholar
  20. 20.
    Bruix J, Qin S, Merle P et al (2017) Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 389:56–66CrossRefPubMedGoogle Scholar
  21. 21.
    Ren Z, Zhu K, Kang H et al (2015) Randomized controlled trial of the prophylactic effect of urea-based cream on sorafenib-associated hand-foot skin reactions in patients with advanced hepatocellular carcinoma. J Clin Oncol 33:894–900CrossRefPubMedGoogle Scholar
  22. 22.
    Reig M, Rimola J, Torres F et al (2013) Postprogression survival of patients with advanced hepatocellular carcinoma: rationale for second-line trial design. Hepatology 58:2023–2031CrossRefPubMedGoogle Scholar
  23. 23.
    Ogasawara S, Chiba T, Ooka Y et al (2016) Post-progression survival in patients with advanced hepatocellular carcinoma resistant to sorafenib. Investig New Drugs 34:255–260CrossRefGoogle Scholar
  24. 24.
    Shao YY, Wu CH, Lu LC et al (2014) Prognosis of patients with advanced hepatocellular carcinoma who failed first-line systemic therapy. J Hepatol 60:313–318CrossRefPubMedGoogle Scholar
  25. 25.
    Kuo YH, Wang JH, Hung CH, et al. (2017) The ALBI grade predicts the prognosis of patients with advanced hepatocellular carcinoma received sorafenib. J Gastroenterol Hepatol. [Epub ahead of print]Google Scholar
  26. 26.
    Ogasawara S, Chiba T, Ooka Y et al (2015) Sorafenib treatment in Child-Pugh A and B patients with advanced hepatocellular carcinoma: safety, efficacy and prognostic factors. Investig New Drugs 33:729–739CrossRefGoogle Scholar
  27. 27.
    Miura K, Satoh M, Kinouchi M et al (2014) The preclinical development of regorafenib for the treatment of colorectal cancer. Expert Opin Drug Discovery 9:1087–1101CrossRefGoogle Scholar
  28. 28.
    Lee IC, Chen YT, Chao Y et al (2015) Determinants of survival after sorafenib failure in patients with BCLC-C hepatocellular carcinoma in real-world practice. Medicine (Baltimore) 94:e688CrossRefGoogle Scholar
  29. 29.
    Llovet JM, Villanueva A, Lachenmayer A et al (2015) Advances in targeted therapies for hepatocellular carcinoma in the genomic era. Nat Rev Clin Oncol 12:408–424CrossRefPubMedGoogle Scholar
  30. 30.
    Ikeda M, Arai Y, Park SJ et al (2013) Prospective study of transcatheter arterial chemo-embolization for unresectable hepatocellular carcinoma: an Asian cooperative study between Japan and Korea. J Vasc Interv Radiol 24:490–500CrossRefPubMedGoogle Scholar
  31. 31.
    Llovet JM, Real MI, Montaña X et al (2002) Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet 359:1734–1739CrossRefPubMedGoogle Scholar
  32. 32.
    Reig M, Torres F, Rodriguez-Lope C et al (2014) Early dermatologic adverse events predict better outcome in HCC patients treated with sorafenib. J Hepatol 61:318–324CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Sadahisa Ogasawara
    • 1
  • Tetsuhiro Chiba
    • 1
  • Yoshihiko Ooka
    • 1
  • Eiichiro Suzuki
    • 1
  • Takahiro Maeda
    • 1
  • Masayuki Yokoyama
    • 1
  • Toru Wakamatsu
    • 1
  • Masanori Inoue
    • 1
  • Tomoko Saito
    • 1
  • Kazufumi Kobayashi
    • 1
  • Soichiro Kiyono
    • 1
  • Masato Nakamura
    • 1
  • Shingo Nakamoto
    • 1
  • Shin Yasui
    • 1
  • Akinobu Tawada
    • 1
  • Makoto Arai
    • 1
  • Tatsuo Kanda
    • 1
  • Hitoshi Maruyama
    • 1
  • Osamu Yokosuka
    • 1
  • Naoya Kato
    • 1
  1. 1.Department of Gastroenterology, Graduate School of MedicineChiba UniversityChibaJapan

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