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

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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.

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Acknowledgments

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

Author information

Author notes

  1. Sadahisa Ogasawara, Yoshihiko Ooka, Norio Itokawa and Masanori Inoue contributed equally to this work.

Authors and Affiliations

  1. Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan

    Sadahisa Ogasawara, Yoshihiko Ooka, 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

  2. Translational Research and Development Center, Chiba University Hospital, Chiba, Japan

    Sadahisa Ogasawara, Kazufumi Kobayashi & Naoya Kato

  3. Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Chiba, Japan

    Norio Itokawa

  4. Department of Gastroenterology, Asahi General Hospital, Asahi, Japan

    Masanori Inoue & Ei Itobayashi

  5. Department of Gastroenterology, Matsudo City General Hospital, Matsudo, Japan

    Shinichiro Okabe

  6. Department of Gastroenterology, Funabashi Municipal Medical Center, Funabashi, Japan

    Atsuyoshi Seki & Hideaki Mizumoto

  7. Department of Gastroenterology, National Hospital Organization Chiba Medical Center, Chiba, Japan

    Yuki Haga & Nobuyuki Sugiura

  8. Department of Gastroenterology, Kimitsu Chuo Hospital, Kisarazu, Japan

    Masamichi Obu & Ryosaku Azemoto

  9. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan

    Masanori Atsukawa

  10. Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan

    Akinobu Tawada & Makoto Arai

  11. Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan

    Tatsuo Kanda

  12. Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan

    Hitoshi Maruyama

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  1. Sadahisa Ogasawara
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  2. Yoshihiko Ooka
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Corresponding author

Correspondence to Sadahisa Ogasawara.

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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.

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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.

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Ogasawara, S., Ooka, Y., Itokawa, N. et al. Sequential therapy with sorafenib and regorafenib for advanced hepatocellular carcinoma: a multicenter retrospective study in Japan. Invest New Drugs 38, 172–180 (2020). https://doi.org/10.1007/s10637-019-00801-8

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  • DOI: https://doi.org/10.1007/s10637-019-00801-8

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