Atezolizumab plus bevacizumab versus lenvatinib or sorafenib in non-viral unresectable hepatocellular carcinoma: an international propensity score matching analysis

被引：73

作者：

Rimini, M. ^{[1
]}

Rimassa, L. ^{[2
,3
]}

Ueshima, K. ^{[4
]}

Burgio, V ^{[1
]}

Shigeo, S. ^{[5
]}

Tada, T. ^{[6
]}

Suda, G. ^{[7
,8
]}

Yoo, C. ^{[9
]}

Cheon, J. ^{[10
]}

Pinato, D. J. ^{[11
,12
]}

Lonardi, S. ^{[13
]}

Scartozzi, M. ^{[14
,15
]}

Iavarone, M. ^{[16
]}

Di Costanzo, G. G. ^{[17
]}

Marra, F. ^{[18
]}

Solda, C. ^{[19
]}

Tamburini, E. ^{[20
]}

Piscaglia, F. ^{[21
]}

Masi, G. ^{[22
,23
]}

Cabibbo, G. ^{[24
]}

Foschi, F. G. ^{[25
]}

Silletta, M. ^{[26
]}

Pressiani, T. ^{[3
]}

Nishida, N. ^{[4
]}

Iwamoto, H. ^{[5
]}

Sakamoto, N. ^{[7
,8
]}

Ryoo, B-Y ^{[9
]}

Chon, H. J. ^{[10
]}

Claudia, F. ^{[11
,12
]}

Niizeki, T. ^{[5
]}

Sho, T. ^{[7
,8
]}

Kang, B. ^{[10
]}

D'Alessio, A. ^{[11
,12
]}

Kumada, T. ^{[27
]}

Hiraoka, A. ^{[28
]}

Hirooka, M. ^{[29
]}

Kariyama, K. ^{[30
]}

Tani, J. ^{[31
]}

Atsukawa, M. ^{[32
]}

Takaguchi, K. ^{[33
]}

Itobayashi, E. ^{[34
]}

Fukunishi, S. ^{[35
]}

Tsuji, K. ^{[36
]}

Ishikawa, T. ^{[37
]}

Tajiri, K. ^{[38
]}

Ochi, H. ^{[39
]}

Yasuda, S. ^{[40
]}

Toyoda, H. ^{[40
]}

Ogawa, C. ^{[41
]}

Nishimur, T. ^{[42
]}

机构：

[1] Univ Vita Salute San Raffaele, IRCCS San Raffaele Sci Inst Hosp, Dept Oncol, Milan, Italy

[2] Humanitas Univ, Dept Biomed Sci, Milan, Italy

[3] IRCCS Humanitas Res Hosp, Humanitas Canc Ctr, Med Oncol & Hematol Unit, Milan, Italy

[4] Kindai Univ, Fac Med, Dept Gastroenterol & Hepatol, Higashiosaka, Osaka, Japan

[5] Kurume Univ, Sch Med, Dept Med, Div Gastroenterol, Kurume, Fukuoka, Japan

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

[7] Dept Gastroenterol & Hepatol, Sapporo, Hokkaido, Japan

[8] Univ Grad Sch Med, Sapporo, Hokkaido, Japan

[9] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, Seoul, South Korea

[10] CHA Univ, CHA Bundang Med Ctr, Sch Med, Dept Med Oncol, Seongnam, South Korea

[11] Hammersmith Hosp, Imperial Coll London, Dept Surg & Canc, London, England

[12] Univ Piemonte Orientale, Dept Translat Med, Novara, Italy

[13] Veneto Inst Oncol IOV IRCCS, Oncol Unit 3, Padua, Italy

[14] Univ Cagliari, Med Oncol, Cagliari, Italy

[15] Univ Hosp Cagliari, Cagliari, Italy

[16] Fdn IRCCS CaGranda Osped Maggiore Policlin Milano, Div Gastroenterol & Hepatol, Milan, Italy

[17] Dept Hepatol, Naples, Italy

[18] Univ Firenze, Dipartimento Med Sperimentale & Clin, Florence, Italy

[19] Veneto Inst Oncol IOV IRCCS, Oncol Unit 1, Padua, Italy

[20] Cardinale Hosp, Dept Oncol & Palliat Care, Naples, Italy

[21] IRCCS Azienda Osped Univ Bologna, Div Internal Med Hepatobiliary & Immunoallerg Dis, Bologna, Italy

[22] Univ Pisa, Dept Translat Res & New Technol Med & Surg, Pisa, Italy

[23] Azienda Osped Univ Pisana, Unit Med Oncol 2, Pisa, Italy

[24] Univ Palermo, Dept Hlth Promot Mother & Child Care, Sect Gastroenterol & Hepatol, PROMISE,Internal Med & Med Specialties, Palermo, Italy

[25] Infermi Hosp, Faenza AUSL ROMAGNA, Internal Med, Ravenna, Italy

[26] Policlin Univ Campus Biomed, Div Med Oncol, Rome, Italy

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

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

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

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

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

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

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

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

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

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

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

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

[39] Japanese Red Cross Matsuyama Hosp, Hepatobiliary Ctr, Matsuyama, Ehime, Japan

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

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

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

[43] Gunma Saiseikai Maebashi Hosp, Dept Gastroenterol, Maebashi, Gumma, Japan

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

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

[46] Hamamatsu Univ, Sch Med, Dept Hepatol, Hamamatsu, Shizuoka, Japan

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

[48] IRCCS San Raffaele Sci Inst, Dept Expt Oncol, Pathol Unit, Milan, Italy

[49] Univ Vita Salute San Raffaele, Sch Med, Milan, Italy

[50] Univ Vita Salute San Raffaele, Liver Ctr, IRCCS San Raffaele Sci Inst, Hepatobiliary Surg Div, Milan, Italy

来源：

ESMO OPEN | 2022年 / 7卷 / 06期

关键词：

advanced HCC; NASH; NAFLD; lenvatinib; sorafenib; atezolizumab; bevacizumab; TO-LYMPHOCYTE RATIO; 1ST-LINE TREATMENT; DOUBLE-BLIND; HCC; CABOZANTINIB; ACTIVATION; THERAPY; NAFLD; NASH;

D O I：

10.1016/j.esmoop.2022.100591

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: A growing body of evidence suggests that non-viral hepatocellular carcinoma (HCC) might benefit less from immunotherapy. Materials and methods: We carried out a retrospective analysis of prospectively collected data from consecutive patients with non-viral advanced HCC, treated with atezolizumab plus bevacizumab, lenvatinib, or sorafenib, in 36 centers in 4 countries (Italy, Japan, Republic of Korea, and UK). The primary endpoint was overall survival (OS) with atezolizumab plus bevacizumab versus lenvatinib. Secondary endpoints were progression-free survival (PFS) with atezolizumab plus bevacizumab versus lenvatinib, and OS and PFS with atezolizumab plus bevacizumab versus sorafenib. For the primary and secondary endpoints, we carried out the analysis on the whole population first, and then we divided the cohort into two groups: non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) population and non-NAFLD/NASH population. Results: One hundred and ninety patients received atezolizumab plus bevacizumab, 569 patients received lenvatinib, and 210 patients received sorafenib. In the whole population, multivariate analysis showed that treatment with lenvatinib was associated with a longer OS [hazard ratio (HR) 0.65; 95% confidence interval (CI) 0.44-0.95; P = 0.0268] and PFS (HR 0.67; 95% CI 0.51-0.86; P = 0.002) compared to atezolizumab plus bevacizumab. In the NAFLD/NASH population, multivariate analysis confirmed that lenvatinib treatment was associated with a longer OS (HR 0.46; 95% CI 0.26-0.84; P = 0.0110) and PFS (HR 0.55; 95% CI 0.38-0.82; P = 0.031) compared to atezolizumab plus bevacizumab. In the subgroup of non-NAFLD/NASH patients, no difference in OS or PFS was observed between patients treated with lenvatinib and those treated with atezolizumab plus bevacizumab. All these results were confirmed following propensity score matching analysis. By comparing patients receiving atezolizumab plus bevacizumab versus sorafenib, no statistically significant difference in survival was observed. Conclusions: The present analysis conducted on a large number of advanced non-viral HCC patients showed for the first time that treatment with lenvatinib is associated with a significant survival benefit compared to atezolizumab plus bevacizumab, in particular in patients with NAFLD/NASH-related HCC.

引用

页数：14

共 50 条

[1] Atezolizumab plus bevacizumab versus lenvatinib or sorafenib in non-viral unresectable hepatocellular carcinoma: An international study
Rimini, M.
Rimassa, L.
Kudo, M.
Shigeo, S.
Toshifumi, T.
Suda, G.
Yoo, C.
Cheon, J.
Lonardi, S.
Scartozzi, M.
Tamburini, E.
Masi, G.
Cascinu, S.
Casadei-Gardini, A.
[J]. ANNALS OF ONCOLOGY, 2022, 33 : S362 - S363
[2] Atezolizumab plus bevacizumab versus lenvatinib or sorafenib in non-viral unresectable hepatocellular carcinoma: An international study.
Casadei-Gardini, Andrea
Rimini, Margherita
Rimassa, Lorenza
Burgio, Valentina
Kudo, Masatoshi
Tada, Toshifumi
Shimose, Shigeo
Suda, Goki
Yoo, Changhoon
Cheon, Jaekyng
Pinato, David J. James
Scartozzi, Mario
Cascinu, Stefano
[J]. JOURNAL OF CLINICAL ONCOLOGY, 2022, 40 (16)
[3] Comparison of Efficacy and Safety of Atezolizumab Plus Bevacizumab and Lenvatinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Propensity Score Matching Analysis
Niizeki, Takashi
Tokunaga, Takayuki
Takami, Yuko
Wada, Yoshiyuki
Harada, Masaru
Shibata, Michihiko
Nakao, Kazuhiko
Sasaki, Ryu
Hirai, Fumihito
Shakado, Satoshi
Yoshizumi, Tomoharu
Itoh, Shinji
Yatsuhashi, Hiroshi
Bekki, Shigemune
Ido, Akio
Mawatari, Seiichi
Honda, Koichi
Sugimoto, Rie
Senju, Takeshi
Takahashi, Hirokazu
Kuwashiro, Takuya
Maeshiro, Tatsuji
Nakamuta, Makoto
Aratake, Yoshifusa
Yamashita, Tsutomu
Otsuka, Yuichiro
Matsumoto, Shuichi
Sohda, Tetsuro
Shimose, Shigeo
Murotani, Kenta
Tanaka, Yasuhito
[J]. TARGETED ONCOLOGY, 2022, 17 (06) : 643 - 653
[4] Comparison of Efficacy and Safety of Atezolizumab Plus Bevacizumab and Lenvatinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Propensity Score Matching Analysis
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Takayuki Tokunaga
Yuko Takami
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Kazuhiko Nakao
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Satoshi Shakado
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Shinji Itoh
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Koichi Honda
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Tsutomu Yamashita
Yuichiro Otsuka
Shuichi Matsumoto
Tetsuro Sohda
Shigeo Shimose
Kenta Murotani
Yasuhito Tanaka
[J]. Targeted Oncology, 2022, 17 : 643 - 653
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Zhao, Chenghao
Xiang, Zhanwang
Li, Mingan
Wang, Haofan
Liu, Huan
Yan, Huzheng
Huang, Mingsheng
[J]. JOURNAL OF HEPATOCELLULAR CARCINOMA, 2023, 10 : 1195 - 1206
[6] Atezolizumab plus bevacizumab versus sorafenib or atezolizumab alone for unresectable hepatocellular carcinoma: A systematic review
Ahmed, Faiza
Onwumeh-Okwundu, Jennifer
Yukselen, Zeynep
Endaya Coronel, Maria-Kassandra
Zaidi, Madiha
Guntipalli, Prathima
Garimella, Vamsi
Gudapati, Sravya
Mezidor, Marc Darlene
Andrews, Kim
Mouchli, Mohamad
Shahini, Endrit
[J]. WORLD JOURNAL OF GASTROINTESTINAL ONCOLOGY, 2021, 13 (11) : 1813 - 1832
[7] Atezolizumab plus bevacizumab versus sorafenib or atezolizumab alone for unresectable hepatocellular carcinoma: A systematic review
Faiza Ahmed
Jennifer Onwumeh-Okwundu
Zeynep Yukselen
Maria-Kassandra Endaya Coronel
Madiha Zaidi
Prathima Guntipalli
Vamsi Garimella
Sravya Gudapati
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Kim Andrews
Mohamad Mouchli
Endrit Shahini
[J]. World Journal of Gastrointestinal Oncology, 2021, 13 (11) : 1813 - 1832
[8] Efficacy of Atezolizumab Plus Bevacizumab Versus Lenvatinib in Patients with Unresectable Hepatocellular Carcinoma: a Meta-analysis
Mah I Kan Changez
Maimoona Khan
Muhammad Uzair
Muhammad Fawad Tahir
Maryam Mohsin
Amna Faiyaz Hussain
Vania Saqib
Muhammad Khizer Molani
Aisha Habib Ahmed
Saad Khalid
[J]. Journal of Gastrointestinal Cancer, 2024, 55 : 467 - 481
[9] Efficacy of Atezolizumab Plus Bevacizumab Versus Lenvatinib in Patients with Unresectable Hepatocellular Carcinoma: a Meta-analysis
Changez, Mah I. Kan
Khan, Maimoona
Uzair, Muhammad
Tahir, Muhammad Fawad
Mohsin, Maryam
Hussain, Amna Faiyaz
Saqib, Vania
Molani, Muhammad Khizer
Ahmed, Aisha Habib
Khalid, Saad
[J]. JOURNAL OF GASTROINTESTINAL CANCER, 2024, 55 (01) : 467 - 481
[10] Survival outcomes from Atezolizumab plus Bevacizumab versus Lenvatinib versus Sorafenib in Child Pugh B unresectable hepatocellular carcinoma patients
Rimini, Margherita
Persano, Mara
Tada, Toshifumi
Suda, Goki
Shigeo, Shimose
Kudo, Masatoshi
Cheon, Jaekyung
Finkelmeier, Fabian
Lim, Ho Yeong
Presa, Jose
Lonardi, Sara
Piscaglia, Fabio
Chon, Hong Jae
Masi, Gianluca
Scartozzi, Mario
Cascinu, Stefano
Casadei-Gardini, Andrea
[J]. JOURNAL OF HEPATOLOGY, 2023, 78 : S592 - S592

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