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Optimal threshold of alpha-fetoprotein response in patients with unresectable hepatocellular carcinoma treated with atezolizumab and bevacizumab

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Summary

Alpha-fetoprotein (AFP) response (relative decline in AFP) is associated with imaging response evaluated by response evaluation criteria in solid tumors ver1.1 (RECIST) and survival in treatment for hepatocellular carcinoma (HCC). However, the optimal threshold of AFP response is still unknown, especially in atezolizumab and bevacizumab (Atez/Bev) treatment. In this prospective multicenter study, we aimed to investigate an optimal threshold of AFP response in Atez/Bev treatment. Out of 284 patients with unresectable HCC who were treated with Atez/Bev, 91 patients with AFP ≥ 10 ng/ml were enrolled in the multicenter study. We investigated the relationship between various AFP response thresholds (relative decline ≥ 20%, ≥ 50%, and ≥ 75%) and treatment response and progression-free survival (PFS). An AFP relative decrease of ≥ 50% was associated with an overall response rate (ORR) with an odds ratio (95% confidence interval [CI]) of 5.7 (1.9–17). Disease control rate (DCR) was associated with an AFP relative decrease of ≥ 20%, with a 100% positive predictive value and a 52.0% sensitivity. AFP relative decreases of ≥ 50% and ≥ 20% were significantly associated with PFS with a hazard ratio (HR) of 5.60 (95% CI: 1.6–19, p = 0.006) and a HR of 4.44 (95% CI: 1.9–10, p < 0.001), respectively. AFP response of ≥ 50% and ≥ 20% were related to ORR and DCR, respectively, and both of these responses were also associated with PFS. AFP can be used as a real-time monitor during Atez/Bev treatment and is helpful for treatment optimization.

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Funding

This work was supported by a Grant-in-Aid from the Japan Agency For Medical Research and Development (JP20fk0210067h0001).

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan

    Nobuharu Tamaki, Masayuki Kurosaki, Yutaka Yasui, Kaoru Tsuchiya & Namiki Izumi

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

    Toshifumi Tada & Shinichiro Nakamura

  3. Center for Liver-Biliary-Pancreatic Disease, Matsuyama Red Cross Hospital, Ehime, Japan

    Hironori Ochi & Toshie Mashiba

  4. Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Osaka, Japan

    Azusa Sakamoto & Hiroyuki Marusawa

  5. Department of Gastroenterology, Oita Red Cross Hospital, Oita, Japan

    Ryoichi Narita

  6. Department of Gastroenterology, Matsue Red Cross Hospital, Shimane, Japan

    Yasushi Uchida

  7. Department of Gastroenterology, Ishinomaki Red Cross Hospital, Miyagi, Japan

    Takehiro Akahane

  8. Department of Gastroenterology, Otsu Red Cross Hospital, Shiga, Japan

    Masahiko Kondo

  9. Department of Gastroenterology, Hiroshima Red Cross Hospital & Atomic-Bomb Survivors Hospital, Hiroshima, Japan

    Nami Mori, Shintaro Takaki & Keiji Tsuji

  10. Department of Gastroenterology, Japanese Red Cross Okayama Hospital, Okayama, Japan

    Haruhiko Kobashi

  11. Department of Gastroenterology, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Aichi, Japan

    Atsunori Kusakabe

  12. Department of Gastroenterology, Masuda Red Cross Hospital, Shimane, Japan

    Koichiro Furuta

  13. Department of Gastroenterology, Maebashi Red Cross Hospital, Gunma, Japan

    Hirotaka Arai

  14. Department of Gastroenterology, Tokushima Red Cross Hospital, Tokushima, Japan

    Michiko Nonogi

  15. Department of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, Kagawa, Japan

    Chikara Ogawa

  16. Department of Gastroenterology, Nasu Red Cross Hospital, Tochigi, Japan

    Takashi Sato

  17. Department of Gastroenterology, Takatsuki Red Cross Hospital, Osaka, Japan

    Takashi Tamada

  18. Department of Gastroenterology, Japanese Red Cross Asahikawa Hospital, Hokkaido, Japan

    Chitomi Hasebe

Authors
  1. Nobuharu Tamaki
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Contributions

Data acquisition, Nobuharu Tamaki, Toshifumi Tada, Masayuki Kurosaki, Yutaka Yasui, Hironori Ochi, Toshie Mashiba, Azusa Sakamoto, Hiroyuki Marusawa, Ryoichi Narita, Yasushi Uchida, Takehiro Akahane, Masahiko Kondo, Nami Mori, Shintaro Takaki, Keiji Tsuji, Haruhiko Kobashi, Atsunori Kusakabe, Koichiro Furuta, Hirotaka Arai, Michiko Nonogi, Shinichiro Nakamura, Chitomi Hasebe, Kaoru Tsuchiya, Namiki Izumi; data analysis, Nobuharu Tamaki, Toshifumi Tada, Masayuki Kurosaki; data interpretation; Nobuharu Tamaki, Toshifumi Tada, Masayuki Kurosaki; drafting of the manuscript, Nobuharu Tamaki; critical revision of the manuscript, all authors; all authors reviewed the manuscript and approved the final submission.

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Correspondence to Masayuki Kurosaki.

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Masayuki Kurosaki and Kaoru Tsuchiya received lecture fees from Chugai. The other authors have no conflicts of interest to declare.

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Tamaki, N., Tada, T., Kurosaki, M. et al. Optimal threshold of alpha-fetoprotein response in patients with unresectable hepatocellular carcinoma treated with atezolizumab and bevacizumab. Invest New Drugs 40, 1290–1297 (2022). https://doi.org/10.1007/s10637-022-01303-w

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