Comparative efficacy and safety of atezolizumab and bevacizumab between hepatocellular carcinoma patients with viral and non-viral infection: A Japanese multicenter observational study

Takeshi Hatanaka; Satoru Kakizaki; Atsushi Hiraoka; Toshifumi Tada; Masashi Hirooka; Kazuya Kariyama; Joji Tani; Masanori Atsukawa; Koichi Takaguchi; Ei Itobayashi; Shinya Fukunishi; Kunihiko Tsuji; Toru Ishikawa; Kazuto Tajiri; Hironori Ochi; Satoshi Yasuda; Hidenori Toyoda; Chikara Ogawa; Takashi Nishimura; Noritomo Shimada; Kazuhito Kawata; Hisashi Kosaka; Takaaki Tanaka; Hideko Ohama; Kazuhiro Nouso; Asahiro Morishita; Akemi Tsutsui; Takuya Nagano; Norio Itokawa; Tomomi Okubo; Taeang Arai; Michitaka Imai; Atsushi Naganuma; Yohei Koizumi; Shinichiro Nakamura; Kouji Joko; Masaki Kaibori; Hiroko Iijima; Yoichi Hiasa; Takashi Kumada; Real-life Practice Experts for HCC (RELPEC) Study Group, and HCC 48 Group (hepatocellular carcinoma experts from 48 clinics in Japan)

doi:10.1002/cam4.5337

Comparative efficacy and safety of atezolizumab and bevacizumab between hepatocellular carcinoma patients with viral and non-viral infection: A Japanese multicenter observational study

Cancer Med. 2023 Mar;12(5):5293-5303. doi: 10.1002/cam4.5337. Epub 2022 Oct 13.

Authors

Takeshi Hatanaka¹, Satoru Kakizaki^{2

3}, Atsushi Hiraoka⁴, Toshifumi Tada⁵, Masashi Hirooka⁶, Kazuya Kariyama⁷, Joji Tani⁸, Masanori Atsukawa⁹, Koichi Takaguchi¹⁰, Ei Itobayashi¹¹, Shinya Fukunishi¹², Kunihiko Tsuji¹³, Toru Ishikawa¹⁴, Kazuto Tajiri¹⁵, Hironori Ochi¹⁶, Satoshi Yasuda¹⁷, Hidenori Toyoda¹⁷, Chikara Ogawa¹⁸, Takashi Nishimura¹⁹, Noritomo Shimada²⁰, Kazuhito Kawata²¹, Hisashi Kosaka²², Takaaki Tanaka⁴, Hideko Ohama⁴, Kazuhiro Nouso⁷, Asahiro Morishita⁸, Akemi Tsutsui¹⁰, Takuya Nagano¹⁰, Norio Itokawa⁹, Tomomi Okubo⁹, Taeang Arai⁹, Michitaka Imai¹⁴, Atsushi Naganuma²³, Yohei Koizumi⁶, Shinichiro Nakamura⁵, Kouji Joko¹⁶, Masaki Kaibori²², Hiroko Iijima¹⁹, Yoichi Hiasa⁶, Takashi Kumada²⁴; Real-life Practice Experts for HCC (RELPEC) Study Group, and HCC 48 Group (hepatocellular carcinoma experts from 48 clinics in Japan)

Affiliations

¹ Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Maebashi, Japan.
² Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan.
³ Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Maebashi, Japan.
⁴ Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan.
⁵ Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan.
⁶ Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan.
⁷ Department of Gastroenterology, Okayama City Hospital, Okayama, Japan.
⁸ Department of Gastroenterology and Hepatology, Kagawa University, Kagawa, Japan.
⁹ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
¹⁰ Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan.
¹¹ Department of Gastroenterology, Asahi General Hospital, Asahi, Japan.
¹² Premier Departmental Research of Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan.
¹³ Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan.
¹⁴ Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan.
¹⁵ Department of Gastroenterology, Toyama University Hospital, Toyama, Japan.
¹⁶ Center for Liver-Biliary-Pancreatic Disease, Matsuyama Red Cross Hospital, Matsuyama, Japan.
¹⁷ Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan.
¹⁸ Department of Gastroenterology, Japanese Red Cross Takamatsu Hospital, Takamatsu, Japan.
¹⁹ Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya, Japan.
²⁰ Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa, Japan.
²¹ Hepatology Division, Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu, Japan.
²² Department of Surgery, Kansai Medical University, Hirakata, Japan.
²³ Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan.
²⁴ Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan.

Abstract

Aim: This study compared the efficacy and safety of atezolizumab and bevacizumab (Atez/Bev) in patients with viral and non-viral infection in clinical settings.

Methods: We conducted the retrospective cohort study of 323 BCLC stage B or C hepatocellular carcinoma (HCC) patients with Child-Pugh class A, and a performance status of 0 or 1 who started Atez/Bev from September 2020 to December 2021 at 22 institutions in Japan. Patients with viral infection was defined as those who were either serum anti-HCV- Ab or HBs-Ag-positive, while patients with non-viral infection was defined as those who were both serum anti-HCV Ab- and HBs-Ag-negative. We constructed a propensity-score-matched cohort to minimize the risk of observable potential confounders.

Results: Propensity score matching produced 126 matched pairs for patients with viral versus non-viral infection. After matching, the significant differences in baseline demographic features did not exist between the two groups. The objective response rate was 20.6% and 24.6% in viral- and non-viral-related HCC patients, respectively, without a significant difference (p = 0.55). The disease control rate was not also significantly different (68.3% vs 69.0%, p = 1.00). The median progression-free survival was 7.0 months (95% confidence interval [CI] 6.0-9.6) and 6.2 months (95% CI 5.1-7.8) in patients with viral and non-viral infection, and the 12-month survival rates were 65.5% (95% CI 50.8-76.8) and 71.7% (95% CI 57.3-81.9) in those with viral and non-viral infection, respectively, which were not significantly different (p = 0.33, p = 0.38). No significant difference in treatment-related adverse events was found between the two groups.

Conclusions: Our etiology-based study demonstrated that Atez/Bev showed good efficacy and safety for HCC patient with non-viral infection as well as those with viral infection.

Keywords: etiology; immune checkpoint inhibitor; non-alcoholic steatohepatitis; propensity score matching; real-world data.

Publication types

Observational Study
Multicenter Study

MeSH terms

Bevacizumab / adverse effects
Carcinoma, Hepatocellular* / pathology
East Asian People
Humans
Liver Neoplasms* / pathology
Retrospective Studies

Substances

atezolizumab
Bevacizumab