Atezolizumab plus bevacizumab versus active surveillance in patients with resected or ablated high-risk hepatocellular carcinoma (IMbrave050): a randomised, open-label, multicentre, phase 3 trial
2023; Elsevier BV; Volume: 402; Issue: 10415 Linguagem: Inglês
10.1016/s0140-6736(23)01796-8
ISSN1474-547X
AutoresShukui Qin, Minshan Chen, Ann‐Lii Cheng, Ahmed O. Kaseb, Masatoshi Kudo, Han Chu Lee, Adam C. Yopp, Jian Zhou, Lu Wang, Xiaoyu Wen, Jeong Heo, Won Young Tak, Shinichiro Nakamura, Kazushi Numata, Thomas Uguen, David Hsiehchen, Edward Cha, Stephen P. Hack, Qinshu Lian, Ning Ma, Jessica Spahn, Yulei Wang, Lyndia C. Wu, Pierce K. H. Chow, Alexander J. Thompson, Mark Danta, Pirooz Poursoltan, Andrew Ddembe Kiberu, Renuka Chittajallu, Siddarth Sood, Rudolf Stauber, Matthias Pinter, Markus Peck‐Radosavljevic, Jochen Decaestecker, Pieter‐Jan Cuyle, Gontran Verset, Hans Van Vlierberghe, Sérgio de Azevedo, Livia Andrade, Ademar Cunha Júnior, Luiza Dib Batista Bugiato Faria, Cheng Tzu Yen, Leandro M. Colli, Jamil Asselah, Petr Kavan, Vladimir Marquez, Mayur Brahmania, Qiang Li, Bao-Cai Xing, Yabing Guo, Zhendong Chen, Haitao Zhao, Tao Peng, Liming Wang, Lu Wang, Hongming Liu, Feixiang Wu, Lun‐Xiu Qin, Qichang Zheng, Jieer Ying, Haitao Li, Tianfu Wen, Shukui Qin, Xiaoyu Wen, Yunpeng Liu, Minshan Chen, Boqing Wang, Yuxian Bai, Yifu He, Hong Zhao, Dong Zhou, Chaoliu Dai, Gao‐Jun Teng, Shuzhong Cui, Yi Gao, Xizhi Zhang, Zheng Lu, Tao Yin, Youming Ding, Weidong Jia, Yongxiang Xia, Beicheng Sun, Qiang Xia, Yufeng Yuan, Hui‐Chuan Sun, Xuetao Shi, A. Guzmán, Luis Corrales, Zdeněk Král, Peter Priester, Eugen Kubala, Jean Frédéric Blanc, Marc Bourlière, Jean Marie Péron, Christophe Borg, Jean‐Pierre Bronowicki, Nathalie Ganne‐Carrié, Thomas Decaens, Thomas Uguen, Alexandra Heurgué, Joerg Trojan, Maria A. González-Carmona, Christoph Roderburg, Thomas Jens Ettrich, Clemens Schotten, Arne Kandulski, Thomas Yau, Stephen L. Chan, Mario Scartozzi, Gianluca Masi, Silvia Fanello, Pier Maria Battezzati, Francesco Leonardi, Michele Ghidini, Kazushi Numata, Manabu Morimoto, Hisashi Hidaka, Kaoru Tsuchiya, Tatsuya Yamashita, Naoya Kato, Masatoshi Kudo, Atsushi Hagihara, Hironori Koga, Tomohiro Arakawa, Ikuo Nakamura, Yusuke Kawamura, Tomokazu Kawaoka, Mitsuo Shimada, Kiyoshi Hasegawa, Hiroyuki Marusawa, Shinchiro Nakamura, Atsushi Hiraoka, Hiromitsu Hayashi, Shin Takeda, Han Chu Lee, Seung Woon Paik, Do Young Kim, Jung Il Lee, Sook‐Hyang Jeong, Won Kim, Won Young Tak, Jeong Heo, Hyeyeong Kim, Hong Jae Chon, Jeong Heo, Seung Kew Yoon, Jung‐Hwan Yoon, Ricardo Villalobos, Jorge Luis Martinez Rodriguez, Victor Oyervides Juarez, Carlos Alberto Hernández, Heinz‐Josef Klümpen, Judith de Vos‐Geelen, Edward Gane, Paola Montenegro, Cesar Torres Mattos, Ewa Janczewska, Maciej Kawecki, Ewa Nowakowska‐Zajdel, А. А. Феденко, Dmitrii Granov, Anna Alyasova, Marina Sekacheva, Evgeny Ledin, Jens Samol, Han Chong Toh, Mariona Calvo Campos, Carlos Gómez Martin, Carlos López, Andrés J. Muñoz Martín, José Luís Calleja, José Luís Montero Álvarez, Maria Reig Monzón, Ignacio Delgado Mingorance, Beatriz Mínguez, Ann‐Lii Cheng, Yi‐Hsiang Huang, Shi‐Ming Lin, Jee‐Fu Huang, Ming‐Lung Yu, Wei‐Wen Su, Krittiya Korphaisarn, Kunlatida Maneenil, Chayanee Samdaengpan, Ekkapong Tharavichitkul, Mustafa Özgüroğlu, Fatih Köse, Hakan Harputluoğlu, Gary L. Buchschacher, Paul J. Thuluvath, Henry Xiong, Mital Patel, Philip J. Gold, Daneng Li, Gabriel A. Brooks, Ashiq Masood, Reema Patel, Ben George, Reena Salgia, Gulam A. Manji, Mary K. Crow, Ahmed O. Kaseb, Matthew Dugan, Kunal C. Kadakia, Adel Kardosh, J.S.S.R. Gibbs, Ashesh P. Shah, Howard A. Burris, David Hsiehchen,
Tópico(s)Hepatitis B Virus Studies
ResumoNo adjuvant treatment has been established for patients who remain at high risk for hepatocellular carcinoma recurrence after curative-intent resection or ablation. We aimed to assess the efficacy of adjuvant atezolizumab plus bevacizumab versus active surveillance in patients with high-risk hepatocellular carcinoma.In the global, open-label, phase 3 IMbrave050 study, adult patients with high-risk surgically resected or ablated hepatocellular carcinoma were recruited from 134 hospitals and medical centres in 26 countries in four WHO regions (European region, region of the Americas, South-East Asia region, and Western Pacific region). Patients were randomly assigned in a 1:1 ratio via an interactive voice-web response system using permuted blocks, using a block size of 4, to receive intravenous 1200 mg atezolizumab plus 15 mg/kg bevacizumab every 3 weeks for 17 cycles (12 months) or to active surveillance. The primary endpoint was recurrence-free survival by independent review facility assessment in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT04102098.The intention-to-treat population included 668 patients randomly assigned between Dec 31, 2019, and Nov 25, 2021, to either atezolizumab plus bevacizumab (n=334) or to active surveillance (n=334). At the prespecified interim analysis (Oct 21, 2022), median duration of follow-up was 17·4 months (IQR 13·9-22·1). Adjuvant atezolizumab plus bevacizumab was associated with significantly improved recurrence-free survival (median, not evaluable [NE]; [95% CI 22·1-NE]) compared with active surveillance (median, NE [21·4-NE]; hazard ratio, 0·72 [adjusted 95% CI 0·53-0·98]; p=0·012). Grade 3 or 4 adverse events occurred in 136 (41%) of 332 patients who received atezolizumab plus bevacizumab and 44 (13%) of 330 patients in the active surveillance group. Grade 5 adverse events occurred in six patients (2%, two of which were treatment related) in the atezolizumab plus bevacizumab group, and one patient (<1%) in the active surveillance group. Both atezolizumab and bevacizumab were discontinued because of adverse events in 29 patients (9%) who received atezolizumab plus bevacizumab.Among patients at high risk of hepatocellular carcinoma recurrence following curative-intent resection or ablation, recurrence-free survival was improved in those who received atezolizumab plus bevacizumab versus active surveillance. To our knowledge, IMbrave050 is the first phase 3 study of adjuvant treatment for hepatocellular carcinoma to report positive results. However, longer follow-up for both recurrence-free and overall survival is needed to assess the benefit-risk profile more fully.F Hoffmann-La Roche/Genentech.
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