Therapeutic efficacy of atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma in patients with Child-Pugh class A or B liver function in real-world clinical practice

Takaaki Tanaka; 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; Takeshi Hatanaka; Satoru Kakizaki; Noritomo Shimada; Kazuhito Kawata; Atsushi Naganuma; Hisashi Kosaka; Hideko Ohama; Kazuhiro Nouso; Asahiro Morishita; Akemi Tsutsui; Takuya Nagano; Norio Itokawa; Tomomi Okubo; Taeang Arai; Michitaka Imai; Yohei Koizumi; Shinichiro Nakamura; Kouji Joko; Hiroko Iijima; Masaki Kaibori; Yoichi Hiasa; Masatoshi Kudo; Takashi Kumada; Real-life Practice Experts for HCC (RELPEC) Study Group; HCC 48 Group (hepatocellular carcinoma experts from 48 clinics in Japan)

doi:10.1111/hepr.13797

Therapeutic efficacy of atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma in patients with Child-Pugh class A or B liver function in real-world clinical practice

Hepatol Res. 2022 Sep;52(9):773-783. doi: 10.1111/hepr.13797. Epub 2022 Jun 11.

Authors

Takaaki Tanaka¹, Atsushi Hiraoka¹, Toshifumi Tada², Masashi Hirooka³, Kazuya Kariyama⁴, Joji Tani⁵, Masanori Atsukawa⁶, Koichi Takaguchi⁷, Ei Itobayashi⁸, Shinya Fukunishi⁹, Kunihiko Tsuji¹⁰, Toru Ishikawa¹¹, Kazuto Tajiri¹², Hironori Ochi¹³, Satoshi Yasuda¹⁴, Hidenori Toyoda¹⁴, Chikara Ogawa¹⁵, Takashi Nishimura¹⁶, Takeshi Hatanaka¹⁷, Satoru Kakizaki¹⁸, Noritomo Shimada¹⁹, Kazuhito Kawata²⁰, Atsushi Naganuma²¹, Hisashi Kosaka²², Hideko Ohama⁹, Kazuhiro Nouso⁴, Asahiro Morishita⁵, Akemi Tsutsui⁷, Takuya Nagano⁷, Norio Itokawa⁶, Tomomi Okubo⁶, Taeang Arai⁶, Michitaka Imai¹¹, Yohei Koizumi³, Shinichiro Nakamura², Kouji Joko¹³, Hiroko Iijima¹⁶, Masaki Kaibori²², Yoichi Hiasa³, Masatoshi Kudo²³, Takashi Kumada²⁴; Real-life Practice Experts for HCC (RELPEC) Study Group; HCC 48 Group (hepatocellular carcinoma experts from 48 clinics in Japan)

Affiliations

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

PMID: 35633504
DOI: 10.1111/hepr.13797

Abstract

Background/aim: Atezolizumab plus bevacizumab (Atez/Bev) treatment is recommended for unresechepatocellular carcinoma (u-HCC) patients classified as Child-Pugh A (CP-A). This study aimed to elucidate the prognosis of patients treated with Atez/Bev, especially CP-A and -B cases.

Materials/methods: From September 2020 to March 2022, 457 u-HCC patients treated with Atez/Bev were enrolled (median age 74 years, male:female = 368:89, CP-A:CP-B = 427:30, Child-Pugh score [CPS] 5:6:7:8:9 = 271:156:21:8:1). Therapeutic response was evaluated using RECIST ver.1.1. Clinical features and prognosis were retrospectively evaluated.

Results: There were no significant differences between CP-A and -B patients in regard to best response (CR:PR:SD:PD = 16:91:194:81 vs. 0:7:13:8, p = 0.739; objective response rate/disease control rate = 28.0%/78.8% vs. 25.0%/71.4%). Analysis performed using inverse probability weighting adjustments of clinical factors other than those related to hepatic reserve function with a p value < 0.10 for comparisons between patients with CP-A and -B showed that the progression-free survival (PFS) rate for CP-A cases was better (6-/12-/18-month: 58.2%/36.1%/27.8% vs. 49.6%/8.7%/non-estimable [NE], p < 0.001), as was overall survival (OS) rate (6-/12-/18-month: 89.9%/71.7%/51.4% versus 63.6%/18.4%/NE; p < 0.001). Median PFS (mPFS) and median OS (mOS) for the CPS-5 were 9.5 months/NE, and 5.1/14.0 months for the CPS-6 (both p < 0.001). Furthermore, for modified albumin-bilirubin grade (mALBI)-1/2a/2b, mPFS was 9.4/8.5/5.3 months (p < 0.001) and mOS was NE/17.8/13.4 months (p < 0.001).

Conclusion: Better hepatic function, such as mALBI grade 1 or 2a are thought to indicate a better condition for obtaining sufficient prognosis with Atez/Bev treatment for u-HCC patients, whereas for CP-B patients, who mainly shown an mALBI grade of 2b or 3, Atez/Bev might have less therapeutic efficacy.

Keywords: Child-Pugh class B; atezolizumab plus bevacizumab; hepatocellular carcinoma; modified albumin-bilirubin grade; prognosis.