Hyperprogressive disease during atezolizumab plus bevacizumab treatment in patients with advanced hepatocellular carcinoma from Japanese real-world practice

Sae Yumita; Sadahisa Ogasawara; Miyuki Nakagawa; Susumu Maruta; Tomomi Okubo; Norio Itokawa; Yotaro Iino; Masamichi Obu; Yuki Haga; Atsuyoshi Seki; Tadayoshi Kogure; Takamasa Ishino; Keita Ogawa; Kisako Fujiwara; Terunao Iwanaga; Naoto Fujita; Takafumi Sakuma; Ryuta Kojima; Hiroaki Kanzaki; Keisuke Koroki; Masanori Inoue; Kazufumi Kobayashi; Soichiro Kiyono; Masato Nakamura; Naoya Kanogawa; Tomoko Saito; Takayuki Kondo; Ryo Nakagawa; Shingo Nakamoto; Ryosuke Muroyama; Tetsuhiro Chiba; Ei Itobayashi; Masanori Atsukawa; Yoshihiro Koma; Ryosaku Azemoto; Kenji Ito; Hideaki Mizumoto; Jun Kato; Naoya Kato

doi:10.1186/s12876-023-02731-5

Hyperprogressive disease during atezolizumab plus bevacizumab treatment in patients with advanced hepatocellular carcinoma from Japanese real-world practice

BMC Gastroenterol. 2023 Mar 31;23(1):101. doi: 10.1186/s12876-023-02731-5.

Authors

Sae Yumita^#¹, Sadahisa Ogasawara^#², Miyuki Nakagawa^#¹, Susumu Maruta³, Tomomi Okubo⁴, Norio Itokawa^{4

5}, Yotaro Iino^{1

6}, Masamichi Obu⁶, Yuki Haga⁷, Atsuyoshi Seki⁸, Tadayoshi Kogure¹, Takamasa Ishino¹, Keita Ogawa¹, Kisako Fujiwara¹, Terunao Iwanaga¹, Naoto Fujita¹, Takafumi Sakuma¹, Ryuta Kojima¹, Hiroaki Kanzaki¹, Keisuke Koroki¹, Masanori Inoue¹, Kazufumi Kobayashi¹, Soichiro Kiyono¹, Masato Nakamura¹, Naoya Kanogawa¹, Tomoko Saito¹, Takayuki Kondo¹, Ryo Nakagawa¹, Shingo Nakamoto¹, Ryosuke Muroyama¹, Tetsuhiro Chiba¹, Ei Itobayashi³, Masanori Atsukawa^{4

5}, Yoshihiro Koma⁶, Ryosaku Azemoto⁶, Kenji Ito⁷, Hideaki Mizumoto⁸, Jun Kato¹, Naoya Kato¹

Affiliations

¹ Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, Japan.
² Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, Japan. ogasawaras@chiba-u.jp.
³ Department of Gastroenterology, Asahi General Hospital, Asahi, Japan.
⁴ Department of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan.
⁵ Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan.
⁶ Department of Gastroenterology, Kimitsu Chuo Hospital, Kisarazu, Japan.
⁷ Department of Gastroenterology, National Hospital Organization Chiba Medical Center, Chiba, Japan.
⁸ Department of Gastroenterology, Funabashi Municipal Medical Center, Funabashi, Japan.

^# Contributed equally.

Abstract

Background: Hyperprogressive disease (HPD) is a phenomenon with greatly accelerated tumor growth and clinical deterioration rates compared to pre-therapy, in patients treated with immune checkpoint inhibitors (ICI). The aim of this study is to clarify the reality of HPD in patients with advanced hepatocellular carcinoma (HCC) who were treated with atezolizumab plus bevacizumab (Atez/Bev) using tumor dynamics.

Methods: Medical records of consecutive patients with advanced HCC who were treated with Atez/Bev were retrospectively reviewed. HPD was defined as a more than two- or fourfold increase in tumor growth rate (TGR) or tumor growth kinetics rate (TGK_R) before and after treatment. Overall survival (OS) and baseline characteristics with or without HPD were analyzed.

Results: A total of 85 patients were included in the analysis. When HPD was defined as a twofold of TGR or TGK_R, 8 patients (8/85, 9.4%) had HPD and 11 had PD without HPD. A total of 5 patients (5/85, 5.9%) were diagnosed with HPD and 14 with PD without HPD when HPD was defined as a fourfold of TGR or TGK_R. No significant difference was observed in the baseline characteristics between HPD and non-HPD.

Conclusion: The prevalence of HPD in patients with advanced HCC treated with Atez/Bev was lower than those treated with nivolumab monotherapy. The HPD mechanism in ICI combined with antibodies targeting vascular endothelial growth factor (VEGF) remains to be elucidated.

Keywords: Atezolizumab and bevacizumab; Hepatocellular carcinoma; Hyperprogressive disease; Immunotherapy.

MeSH terms

Bevacizumab / therapeutic use
Carcinoma, Hepatocellular* / drug therapy
Carcinoma, Hepatocellular* / pathology
Disease Progression
East Asian People
Humans
Liver Neoplasms* / drug therapy
Liver Neoplasms* / pathology
Retrospective Studies
Vascular Endothelial Growth Factor A

Substances

atezolizumab
Bevacizumab
Vascular Endothelial Growth Factor A