Association of early bevacizumab interruption with efficacy of atezolizumab plus bevacizumab for advanced hepatocellular carcinoma: A landmark analysis

被引：33

作者：

Hatanaka, Takeshi ^{[1
]}

Hiraoka, Atsushi ^{[2
]}

Tada, Toshifumi ^{[3
]}

Hirooka, Masashi ^{[4
]}

Kariyama, Kazuya ^{[5
]}

Tani, Joji ^{[6
]}

Atsukawa, Masanori ^{[7
]}

Takaguchi, Koichi ^{[8
]}

Itobayashi, Ei ^{[9
]}

Fukunishi, Shinya ^{[10
]}

Tsuji, Kunihiko ^{[11
]}

Ishikawa, Toru ^{[12
]}

Tajiri, Kazuto ^{[13
]}

Ochi, Hironori ^{[14
]}

Yasuda, Satoshi ^{[15
]}

Toyoda, Hidenori ^{[15
]}

Ogawa, Chikara ^{[16
]}

Nishimura, Takashi ^{[17
]}

Kakizaki, Satoru ^{[18
]}

Shimada, Noritomo ^{[19
]}

Kawata, Kazuhito ^{[20
]}

Tanaka, Takaaki ^{[2
]}

Ohama, Hideko ^{[10
]}

Nouso, Kazuhiro ^{[5
]}

Morishita, Asahiro ^{[6
]}

Tsutsui, Akemi ^{[8
]}

Nagano, Takuya ^{[8
]}

Itokawa, Norio ^{[7
]}

Okubo, Tomomi ^{[7
]}

Arai, Taeang ^{[7
]}

Imai, Michitaka ^{[12
]}

Naganuma, Atsushi ^{[21
]}

Koizumi, Yohei ^{[4
]}

Nakamura, Shinichiro ^{[3
]}

Joko, Kouji ^{[14
]}

Iijima, Hiroko ^{[17
]}

Hiasa, Yoichi ^{[4
]}

Kumada, Takashi ^{[22
]}

机构：

[1] Gunma Saiseikai Maebashi Hosp, Dept Gastroenterol, Kamishindenmachi 564-1, Maebashi, Gumma 3710821, Japan

[2] Ehime Prefectural Cent Hosp, Gastroenterol Ctr, Matsuyama, Ehime, Japan

[3] Japanese Red Cross Himeji Hosp, Dept Internal Med, Himeji, Hyogo, Japan

[4] Ehime Univ, Dept Gastroenterol & Metabol, Grad Sch Med, Matsuyama, Ehime, Japan

[5] Okayama City Hosp, Dept Gastroenterol, Okayama, Japan

[6] Kagawa Univ, Dept Gastroenterol & Hepatol, Takamatsu, Kagawa, Japan

[7] Nippon Med Sch, Dept Internal Med, Div Gastroenterol & Hepatol, Tokyo, Japan

[8] Kagawa Prefectural Cent Hosp, Dept Hepatol, Takamatsu, Kagawa, Japan

[9] Asahi Gen Hosp, Dept Gastroenterol, Asahi, Japan

[10] Osaka Med & Pharmaceut Univ, Premier Dept Res Med, Takatsuki, Osaka, Japan

[11] Teine Keijinkai Hosp, Ctr Gastroenterol, Sapporo, Hokkaido, Japan

[12] Saiseikai Niigata Hosp, Dept Gastroenterol, Niigata, Japan

[13] Toyama Univ Hosp, Dept Gastroenterol, Toyama, Japan

[14] Matsuyama Red Cross Hosp, Ctr Liver Biliary Pancreat Dis, Matsuyama, Ehime, Japan

[15] Ogaki Municipal Hosp, Dept Gastroenterol & Hepatol, Ogaki, Japan

[16] Japanese Red Cross Takamatsu Hosp, Dept Gastroenterol, Takamatsu, Kagawa, Japan

[17] Hyogo Coll Med, Dept Internal Med, Div Gastroenterol & Hepatol, Nishinomiya, Hyogo, Japan

[18] Natl Hosp Org Takasaki Gen Med Ctr, Dept Clin Res, Takasaki, Gumma, Japan

[19] Otakanomori Hosp, Div Gastroenterol & Hepatol, Kashiwa, Chiba, Japan

[20] Hamamatsu Univ Sch Med, Dept Internal Med 2, Nepatol Div, Hamamatsu, Shizuoka, Japan

[21] Natl Hosp Org Takasaki Gen Med Ctr, Dept Gastroenterol, Takasaki, Gumma, Japan

[22] Gifu Kyoritsu Univ, Dept Nursing, Ogaki, Japan

来源：

HEPATOLOGY RESEARCH | 2022年 / 52卷 / 05期

关键词：

adverse events; atezolizumab plus bevacizumab; hepatocellular carcinoma; interruption; landmark analysis; ENDOTHELIAL GROWTH-FACTOR; SORAFENIB; MATURATION; CELLS;

D O I：

10.1111/hepr.13748

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Aim The present study focused on the association of early bevacizumab (Bev) interruption with the clinical outcome of atezolizumab plus bevacizumab. Methods This retrospective study included 239 patients with advanced hepatocellular carcinoma receiving atezolizumab/Bev from September 2020 to June 2021 at 16 different institutions in Japan. We conducted a 9-week landmark analysis to investigate the association of Bev interruption due to adverse events with the therapeutic efficacy. Results The median age was 73.0 (68.0-80.0) years old, with 195 (81.6%) men. The objective response rate was significantly higher in patients without Bev interruption than in those with it (34.5% vs. 17.3%, p = 0.038). The median progression-free survival (PFS) was 6.5 months (95% confidence interval [CI] 4.5-9.7) and 9.0 months (95% CI 7.1-not applicable) in patients with and without Bev interruption, respectively, with statistical significance (p = 0.021). The 12-month overall survival (OS) rates in patients with and without Bev interruption were 49.4% (CI 27.7%-67.9%) and 82.2% (95% CI 70.3%-89.6%), respectively, showing a significant difference (p = 0.004). The presence of Bev interruption was a significant factor associated with the PFS (p = 0.021) and OS (p = 0.008). A multivariate analysis showed that modified albumin-bilirubin 2b (p < 0.001) and later-line treatment (p = 0.018) were unfavorable factors associated with Bev interruption. Liver injury, appetite loss, protein urea, and ascites or hepatic edema were more frequently found in patients with Bev interruption than in those without it. Conclusions Early Bev interruption was an unfavorable factor associated with the PFS and OS. Good liver function and treatment settings may be associated with maintaining Bev treatment.

引用

页码：462 / 470

页数：9

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