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Efficacy and safety of atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma patients with esophageal–gastric varices

  • Original Article―Liver, Pancreas, and Biliary Tract
  • Published:
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Abstract

Background

Bevacizumab inhibits vascular endothelial growth factor-A (VEGF-A), though is known to increase bleeding risk as an adverse event (AE). This study examined whether atezolizumab/bevacizumab (Atez/Bev) for unresectable hepatocellular carcinoma (uHCC) can be used for patients with esophageal–gastric varices (EGV).

Methods

From October 2020 to December 2022, 506 uHCC patients (median 74 years) underwent an upper gastrointestinal endoscopy examination were enrolled, after exclusion of those with portal vein tumor thrombus (PVTT). Patients with EGV (≧ F1) were defined as EGV positive, and the cohort was divided into non-EGV (n = 355) and EGV (n = 151). Before introducing Atez/Bev, endoscopic treatment was performed, when necessary. Prognosis was evaluated, retrospectively.

Results

The EGV group had significantly worse hepatic function, lower platelet count, elevated alpha-fetoprotein, and lower rate of extrahepatic metastasis, and lower rate of first-line use (each P < 0.05) than the other. However, progression-free survival (PFS) was also not a significantly difference between the EGV and non-EGV groups in analyses with (PFS rate at 6/12/18 months: 60%/38%/30% vs. 65%/46%/34%, P = 0.29) or without inverse probability weighting adjustment [median: 10.6 months (95% CI 8.3–14.0) vs. 10.5 months (95% CI 7.8–13.7), P = 0.79]. As for AEs, diarrhea was more frequent in the EGV group (≧ G3: 2.0% vs. 0.3%, P = 0.036), while no significant difference was noted for EGV hemorrhage (≧ G3: 1.3% vs. 0.6%, P = 0.345). Of 28 patients who underwent endoscopic treatments before introducing Atez/Bev, none showed EGV-associated hemorrhage.

Conclusions

Atez/Bev might be an effective therapeutic option in patients with EGV, when appropriate endoscopic treatment for EGV is performed.

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Data availability

Due to the nature of this research, the participants could not be contacted regarding whether the findings could be shared publicly, and thus, supporting data, including datasets generated and/or analyzed for the current study, are not publicly available.

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Funding

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Author information

Authors and Affiliations

  1. Gastroenterology Center, Ehime Prefectural Central Hospital, 83 Kasuga-cho, Matsuyama, Ehime, 790-0024, Japan

    Fujimasa Tada, Atsushi Hiraoka & Hideko Ohama

  2. Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan

    Toshifumi Tada & Shinichiro Nakamura

  3. Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan

    Masashi Hirooka, Yohei Koizumi & Yoichi Hiasa

  4. Department of Hepatology, Okayama City Hospital, Okayama, Japan

    Kazuya Kariyama & Kazuhiro Nouso

  5. Department of Gastroenterology and Hepatology, Kagawa University, Takamatsu, Kagawa, Japan

    Joji Tani & Asahiro Morishita

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

    Masanori Atsukawa, Norio Itokawa, Tomomi Okubo & Taeang Arai

  7. Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan

    Koichi Takaguchi, Akemi Tsutsui & Takuya Nagano

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

    Ei Itobayashi

  9. Department of Gastroenterology, Osaka Medical and Pharmaceutical University, Osaka, Japan

    Shinya Fukunishi, Keisuke Yokohama & Hiroki Nishikawa

  10. Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan

    Kunihiko Tsuji

  11. Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan

    Toru Ishikawa & Michitaka Imai

  12. Department of Gastroenterology, Toyama University Hospital, Toyama, Japan

    Kazuto Tajiri

  13. Center of Liver–Biliary–Pancreatic Disease, Matsuyama Red Cross Hospital, Matsuyama, Japan

    Hironori Ochi

  14. Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan

    Hidenori Toyoda

  15. Department of Gastroenterology, Japanese Red Cross Takamatsu Hospital, Takamatsu, Japan

    Chikara Ogawa

  16. Department of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya, Japan

    Takashi Nishimura & Hiroko Iijima

  17. Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Maebashi, Gunma, Japan

    Takeshi Hatanaka

  18. Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan

    Satoru Kakizaki

  19. Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa, Japan

    Noritomo Shimada

  20. Hepatology Division, Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Kazuhito Kawata

  21. Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan

    Atsushi Naganuma

  22. Department of Surgery, Kansai Medical University, Hirakata, Japan

    Hisashi Kosaka & Masaki Kaibori

  23. Department of Hepatology, Himeji St. Mary’s Hospital, Himeji, Japan

    Tomomitsu Matono

  24. Division of Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka, Japan

    Hidekatsu Kuroda

  25. Department of Gastroenterology, Hanwa Memorial Hospital, Osaka, Japan

    Yutaka Yata

  26. Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan

    Takashi Kumada

Authors
  1. Fujimasa Tada
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  2. Atsushi Hiraoka
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  3. Toshifumi Tada
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  4. Masashi Hirooka
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  5. Kazuya Kariyama
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  6. Joji Tani
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  7. Masanori Atsukawa
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  10. Shinya Fukunishi
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  11. Kunihiko Tsuji
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  12. Toru Ishikawa
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  13. Kazuto Tajiri
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  14. Hironori Ochi
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  15. Hidenori Toyoda
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  17. Takashi Nishimura
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  18. Takeshi Hatanaka
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  19. Satoru Kakizaki
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  23. Hisashi Kosaka
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  28. Kazuhiro Nouso
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  31. Takuya Nagano
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  32. Norio Itokawa
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  33. Tomomi Okubo
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  34. Taeang Arai
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  35. Keisuke Yokohama
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  37. Michitaka Imai
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  38. Yohei Koizumi
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  39. Shinichiro Nakamura
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  40. Hiroko Iijima
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  41. Masaki Kaibori
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  42. Yoichi Hiasa
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  43. Takashi Kumada
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Consortia

the Real-life Practice Experts for HCC (RELPEC) Study Group, HCC 48 Group (hepatocellular carcinoma experts from 48 clinics in Japan)

Contributions

AH and TK conceived the study, and participated in its design and coordination. AH, TT, MH, KK, JT, MA, KT, EI, SF, KT, TI, KT, HO, SY, HT, CO, TN, TH, SK, NS, KK, AN, HK, TM, HK, YY, HO, FT, KN, AM, AT, TN, NI, TO, TA, KY, HN, MI, YK, SN, HI, MK, YH, and TK performed data curation. FT and AH performed statistical analyses and interpretation. FT and AH drafted the text. All authors have read and approved the final version of the manuscript.

Corresponding author

Correspondence to Atsushi Hiraoka.

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Conflict of interest

Atsushi Hiraoka, MD, PhD: lecture fees; Chugai, Bayer, and Eli Lilly. Takashi Kumada, MD, PhD: lecture fees; Eisai. Toshifumi Tada MD, PhD: AbbVie, Eisai, and Chugai. Takeshi Hatanaka MD, PhD: Eisai. None of the other authors have potential conflicts of interest to declare.

Ethical approval

The entire study protocol was approved by the Institutional Ethics Committee of Ehime Prefectural Central Hospital (No. 2022-46). After receiving official approval, this study was conducted as a retrospective analysis of database records based on the Guidelines for Clinical Research issued by the Ministry of Health and Welfare of Japan. All procedures were done in accordance with the Declaration of Helsinki. The data were made anonymous before analysis to protect patient privacy. Written informed consent was obtained from all patients before treatment and this study received ethical approval for use of an opt-out methodology based on low risk to the participants.

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Tada, F., Hiraoka, A., Tada, T. et al. Efficacy and safety of atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma patients with esophageal–gastric varices. J Gastroenterol 58, 1134–1143 (2023). https://doi.org/10.1007/s00535-023-02026-2

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