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Sequential therapy with sorafenib and regorafenib for advanced hepatocellular carcinoma: a multicenter retrospective study in Japan

  • Sadahisa OgasawaraEmail author
  • Yoshihiko Ooka
  • Norio Itokawa
  • Masanori Inoue
  • Shinichiro Okabe
  • Atsuyoshi Seki
  • Yuki Haga
  • Masamichi Obu
  • Masanori Atsukawa
  • Ei Itobayashi
  • Hideaki Mizumoto
  • Nobuyuki Sugiura
  • Ryosaku Azemoto
  • Kengo Kanayama
  • Hiroaki Kanzaki
  • Susumu Maruta
  • Takahiro Maeda
  • Yuko Kusakabe
  • Masayuki Yokoyama
  • Kazufumi Kobayashi
  • Soichiro Kiyono
  • Masato Nakamura
  • Tomoko Saito
  • Eiichiro Suzuki
  • Shingo Nakamoto
  • Shin Yasui
  • Akinobu Tawada
  • Tetsuhiro Chiba
  • Makoto Arai
  • Tatsuo Kanda
  • Hitoshi Maruyama
  • Naoya Kato
SHORT REPORT
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Summary

Background Conversion from sorafenib to regorafenib is primarily an evidence-based treatment strategy in patients with advanced hepatocellular carcinoma (HCC). This study aimed to assess the safety and efficacy of sequential therapy with sorafenib and regorafenib in patients with advanced HCC by analysis of outcomes in clinical practice with the aim to complement phase III findings. Methods The medical records of patients with advanced HCC receiving regorafenib were retrieved to collect data on sorafenib administration at seven Japanese institutions. Radiological responses and adverse events were evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1 and the Common Terminology Criteria for Adverse Events version 4.0, respectively. Results Before March 2018, 44 patients were administered regorafenib for advanced HCC. The median sorafenib treatment duration was 8.4 months. The most common adverse events were similar to those reported by the RESORCE trial. The median overall survival (OS) was 17.3 months (95% confidence interval [CI] 11.4–22.9), and 17 of 37 patients (45.9%) discontinued regorafenib and received sequential systemic therapy after regorafenib. These patients had significantly longer OS than those who were treated by the best supportive care or sub-optimal therapy (not reached versus 8.7 months [95% CI 5.8–11.7]; P < 0.001). Conclusion The results based on Japanese clinical practices verified the tolerability of regorafenib in advanced HCC. Major regorafenib-associated adverse events were similar to those related to sorafenib. OS was significantly longer than expected, which might be associated with the sequential systemic therapies after regorafenib, mainly lenvatinib.

Keywords

Hepatocellular carcinoma Sorafenib Regorafenib Lenvatinib Second-line RESORCE 

Notes

Acknowledgments

These authors would like to thank Enago (www.enago.jp) for the English language review.

Compliance with ethical standards

Conflict of interest

Sadahisa Ogasawara received grant support, advisory fee and honoraria from Bayer and Eisai. Naoya Kato received grant support, advisory fee and honoraria from Bayer and Eisai. 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.

Research involving human participants

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.

Supplementary material

10637_2019_801_MOESM1_ESM.pdf (322 kb)
ESM 1 (PDF 321 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Sadahisa Ogasawara
    • 1
    • 2
    Email author
  • Yoshihiko Ooka
    • 1
  • Norio Itokawa
    • 3
  • Masanori Inoue
    • 4
  • Shinichiro Okabe
    • 5
  • Atsuyoshi Seki
    • 6
  • Yuki Haga
    • 7
  • Masamichi Obu
    • 8
  • Masanori Atsukawa
    • 9
  • Ei Itobayashi
    • 4
  • Hideaki Mizumoto
    • 6
  • Nobuyuki Sugiura
    • 7
  • Ryosaku Azemoto
    • 8
  • Kengo Kanayama
    • 1
  • Hiroaki Kanzaki
    • 1
  • Susumu Maruta
    • 1
  • Takahiro Maeda
    • 1
  • Yuko Kusakabe
    • 1
  • Masayuki Yokoyama
    • 1
  • Kazufumi Kobayashi
    • 1
    • 2
  • Soichiro Kiyono
    • 1
  • Masato Nakamura
    • 1
  • Tomoko Saito
    • 1
  • Eiichiro Suzuki
    • 1
  • Shingo Nakamoto
    • 1
  • Shin Yasui
    • 1
  • Akinobu Tawada
    • 1
    • 10
  • Tetsuhiro Chiba
    • 1
  • Makoto Arai
    • 1
    • 10
  • Tatsuo Kanda
    • 1
    • 11
  • Hitoshi Maruyama
    • 1
    • 12
  • Naoya Kato
    • 1
    • 2
  1. 1.Department of Gastroenterology, Graduate School of MedicineChiba UniversityChibaJapan
  2. 2.Translational Research and Development CenterChiba University HospitalChibaJapan
  3. 3.Division of Gastroenterology, Department of Internal MedicineNippon Medical School Chiba Hokusoh HospitalChibaJapan
  4. 4.Department of GastroenterologyAsahi General HospitalAsahiJapan
  5. 5.Department of GastroenterologyMatsudo City General HospitalMatsudoJapan
  6. 6.Department of GastroenterologyFunabashi Municipal Medical CenterFunabashiJapan
  7. 7.Department of GastroenterologyNational Hospital Organization Chiba Medical CenterChibaJapan
  8. 8.Department of GastroenterologyKimitsu Chuo HospitalKisarazuJapan
  9. 9.Division of Gastroenterology and Hepatology, Department of Internal MedicineNippon Medical SchoolTokyoJapan
  10. 10.Department of Medical Oncology, Graduate School of MedicineChiba UniversityChibaJapan
  11. 11.Division of Gastroenterology and Hepatology, Department of MedicineNihon University School of MedicineTokyoJapan
  12. 12.Department of GastroenterologyJuntendo University School of MedicineTokyoJapan

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