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Early experience of atezolizumab plus bevacizumab therapy in Japanese patients with unresectable hepatocellular carcinoma in real-world practice

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Summary

Background. We aimed to investigate the efficacy and safety of atezolizumab plus bevacizumab therapy in patients with unresectable hepatocellular carcinoma (u-HCC) based on whether they had previously received systemic therapy, as well as the association of atezolizumab plus bevacizumab with early alpha-fetoprotein (AFP) response in real-world practice. Methods. A total of 52 patients with u-HCC were treated with atezolizumab plus bevacizumab between October 2020 and April 2021. The Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST were used to evaluate radiological responses. Results. The patients received atezolizumab plus bevacizumab as 1st-line (n = 23), 2nd-line (n = 16), 3rd-line (n = 6), 4th-line (n = 3), 5th-line (n = 3), or 6th-line (n = 1) therapy. According to RECIST, the objective response rate (ORR) and disease control rate (DCR) in all patients were 15.4% and 57.7%. In the 1st-line patients, ORR and DCR based on RECIST 1.1 were 27.3% and 81.8%. The median time to progression (TTP) assessed by RECIST was significantly longer among patients receiving atezolizumab plus bevacizumab as 1st-line therapy than in patients receiving atezolizumab plus bevacizumab as later-line therapy (P < 0.001). Patients with an AFP response (reduction ≥ 20% from baseline) at 6 weeks had a significantly longer TTP assessed by RECIST than those without an AFP response (P = 0.02). Conclusion. Patients who received atezolizumab plus bevacizumab as 1st-line therapy had better clinical outcome than those who received atezolizumab plus bevacizumab in later lines. The AFP response at 6 weeks could be a predictor of disease progression.

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Data availability

The data presented in this study are available upon request from the corresponding author.

Code availability

Not applicable.

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Acknowledgements

We thank the patients and medical staff who contributed to this study.

Funding

This study was supported by a grant-in-aid from the Japanese Ministry of Health, Labour and Welfare and from the Japan Agency for Medical Research and Development (JP20fk0210067h0001).

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Author notes

  1. Yuka Hayakawa and Kaoru Tsuchiya these two authors contributed equally to this work

Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, 1-26-1, Kyonan-cho, Musashino-shi, Tokyo, 180-8610, Japan

    Yuka Hayakawa, Kaoru Tsuchiya, Masayuki Kurosaki, Yutaka Yasui, Shun Kaneko, Yuki Tanaka, Shun Ishido, Kento Inada, Sakura Kirino, Koji Yamashita, Tsubasa Nobusawa, Hiroaki Matsumoto, Tatsuya Kakegawa, Mayu Higuchi, Kenta Takaura, Shohei Tanaka, Chiaki Maeyashiki, Nobuharu Tamaki, Hiroyuki Nakanishi, Jun Itakura, Yuka Takahashi & Namiki Izumi

  2. Department of Gastroenterology and Hepatology, Tokyo Medical Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan

    Yuka Hayakawa, Shun Kaneko, Shun Ishido, Kento Inada, Sakura Kirino, Tsubasa Nobusawa, Hiroaki Matsumoto, Shohei Tanaka, Chiaki Maeyashiki, Yasuhiro Asahina & Ryuichi Okamoto

  3. Division of Gastroenterology and Hepatology, Department of Medicine, NAFLD Research Center, University of California San Diego, La Jolla, CA92093, USA

    Nobuharu Tamaki

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  1. Yuka Hayakawa
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Contributions

Study design: Yuka Hayakawa and Kaoru Tsuchiya Data collection: Yuka Hayakawa, Kaoru Tsuchiya, Masayuki Kurosaki, Yutaka Yasui, Shun Kaneko, Yuki Tanaka, Shun Ishido, Kento Inada, Sakura Kirino, Koji Yamashita, Tsubasa Nobusawa, Hiroaki Matsumoto, Tatsuya Kakegawa, Mayu Higuchi, Kenta Takaura, Shohei Tanaka, Chiaki Maeyashiki, Nobuharu Tamaki, Hiroyuki Nakanishi, Jun Itakura, Yuka Takahashi and Namiki Izumi Data analysis: Yuka Hayakawa and Kaoru Tsuchiya Data interpretation: Yuka Hayakawa, Kaoru Tsuchiya, Masayuki Kurosaki, Shun Kaneko, Yutaka Yasui, Yasuhiro Asahina, Ryuichi Okamoto and Namiki Izumi Manuscript writing: Yuka Hayakawa and Kaoru Tsuchiya Manuscript revision: Masayuki Kurosaki, Shun Kaneko, Yutaka Yasui, Yasuhiro Asahina, Ryuichi Okamoto and Namiki Izumi All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Yuka Hayakawa.

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Ethical approval

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of Musashino Red Cross Hospital (No. 28077).

Informed consent

Informed consent was obtained from all subjects involved in the study.

Conflict of interest

Kaoru Tsuchiya, Masayuki Kurosaki, and Namiki Izumi received advisory board fees and honoraria from the speakers’ bureau from Bayer, Eisai, Eli Lilly Japan, and Roche. The Japanese Ministry of Health, Labour and Welfare had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

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Hayakawa, Y., Tsuchiya, K., Kurosaki, M. et al. Early experience of atezolizumab plus bevacizumab therapy in Japanese patients with unresectable hepatocellular carcinoma in real-world practice. Invest New Drugs 40, 392–402 (2022). https://doi.org/10.1007/s10637-021-01185-4

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