Lenvatinib: established and promising drug for the treatment of advanced hepatocellular carcinoma

被引:16
作者
Catalano, Martina [1 ]
Casadei-Gardini, Andrea [2 ]
Vannini, Gianmarco [1 ]
Campani, Claudia [3 ]
Marra, Fabio [3 ,4 ]
Mini, Enrico [5 ]
Roviello, Giandomenico [5 ]
机构
[1] Univ Florence, Sch Human Hlth Sci, Florence, Italy
[2] Univ Vita Salute, San Raffaele Hosp IRCCS, Dept Med Oncol, Milan, Italy
[3] Univ Florence, Dept Expt & Clin Med, Florence, Italy
[4] Excellence Ctr Res Transfer Snd High Educ DenoTHE, Florence, Italy
[5] Univ Florence, Dept Hlth Sci, Florence, Italy
关键词
Advanced HCC; combination therapy; lenvatinib; tyrosine kinase inhibitor; FIBROBLAST-GROWTH-FACTOR; ATEZOLIZUMAB PLUS BEVACIZUMAB; TYROSINE KINASE INHIBITOR; ADVERSE EVENTS; TUMOR MICROENVIRONMENT; ANTITUMOR ACTIVITIES; T-CELLS; SORAFENIB; SURVIVAL; EFFICACY;
D O I
10.1080/17512433.2021.1958674
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction : The evolving therapeutic landscape of advanced hepatocellular carcinoma (HCC) includes the increasing implementation of target-therapy and immunotherapy. Lenvatinib, a multi-target tyrosine kinase inhibitor (TKI), is an emerging first-line therapy for hepatocellular carcinoma. Its approval has changed the scenario of first-line therapies for advanced HCC, where just sorafenib proved clinical efficacy for over a decade. Areas covered : The current evidence on the role of lenvatinib for patients with advanced HCC is reviewed in this article. Particularly, therapeutic mechanisms and clinical efficacy of lenvatinib are summarized and the management of adverse events is discussed. In addition, future perspectives on the emerging role of combine therapy for HCC are highlighted. Expert Opinion In the first line, lenvatinib was found to be non-inferior to sorafenib for overall survival, with significantly better progression-free survival and objective response rate. Immune checkpoint inhibitors (ICIs) are now part of HCC treatment, and recently the combination of atezolizumab plus bevacizumab has become the recommended standard of care first-line therapy for selected patients. The antitumor and immunomodulatory activities that lenvatinib shows in preclinical studies, and the positive outcomes achieved using a combination of lenvatinib plus ICIs, open new perspectives for advanced HCC treatment.
引用
收藏
页码:1353 / 1365
页数:13
相关论文
共 125 条
[111]   Lenvatinib-Induced Tumor-Related Hemorrhages in Patients with Large Hepatocellular Carcinomas [J].
Uchida-Kobayashi, Sawako ;
Kageyama, Ken ;
Yamamoto, Akira ;
Ikenaga, Hiroko ;
Yoshida, Kanako ;
Kotani, Kohei ;
Kimura, Kenjiro ;
Odagiri, Naoshi ;
Hagihara, Atsushi ;
Fujii, Hideki ;
Enomoto, Masaru ;
Tamori, Akihiro ;
Kubo, Shoji ;
Miki, Yukio ;
Kawada, Norifumi .
ONCOLOGY, 2021, 99 (03) :186-191
[112]   Impact of Baseline ALBI Grade on the Outcomes of Hepatocellular Carcinoma Patients Treated with Lenvatinib: A Multicenter Study [J].
Ueshima, Kazuomi ;
Nishida, Naoshi ;
Hagiwara, Satoru ;
Aoki, Tomoko ;
Minami, Tomohiro ;
Chishina, Hirokazu ;
Takita, Masahiro ;
Minami, Yasunori ;
Ida, Hiroshi ;
Takenaka, Mamoru ;
Sakurai, Toshiharu ;
Watanabe, Tomohiro ;
Morita, Masahiro ;
Ogawa, Chikara ;
Hiraoka, Atsushi ;
Johnson, Philip ;
Kudo, Masatoshi .
CANCERS, 2019, 11 (07)
[113]   The concept of therapeutic hierarchy for patients with hepatocellular carcinoma: A multicenter cohort study [J].
Vitale, Alessandro ;
Farinati, Fabio ;
Pawlik, Timothy M. ;
Frigo, Anna Chiara ;
Giannini, Edoardo G. ;
Napoli, Lucia ;
Ciccarese, Francesco ;
Rapaccini, Gian Ludovico ;
Di Marco, Maria ;
Caturelli, Eugenio ;
Zoli, Marco ;
Borzio, Franco ;
Sacco, Rodolfo ;
Cabibbo, Giuseppe ;
Virdone, Roberto ;
Marra, Fabio ;
Felder, Martina ;
Morisco, Filomena ;
Benvegnu, Luisa ;
Gasbarrini, Antonio ;
Svegliati-Baroni, Gianluca ;
Foschi, Francesco Giuseppe ;
Missale, Gabriele ;
Masotto, Alberto ;
Nardone, Gerardo ;
Colecchia, Antonio ;
Bernardi, Mauro ;
Trevisani, Franco ;
Cillo, Umberto .
LIVER INTERNATIONAL, 2019, 39 (08) :1478-1489
[114]  
Voron T., 2014, FRONTIERS ONCOLOGY
[115]   VEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors [J].
Voron, Thibault ;
Colussi, Orianne ;
Marcheteau, Elie ;
Pernot, Simon ;
Nizard, Mevyn ;
Pointet, Anne-Laure ;
Latreche, Sabrina ;
Bergaya, Sonia ;
Benhamouda, Nadine ;
Tanchot, Corinne ;
Stockmann, Christian ;
Combe, Pierre ;
Berger, Anne ;
Zinzindohoue, Franck ;
Yagita, Hideo ;
Tartour, Eric ;
Taieb, Julien ;
Terme, Magali .
JOURNAL OF EXPERIMENTAL MEDICINE, 2015, 212 (02) :139-148
[116]   Efficacy and safety of lenvatinib for patients with advanced hepatocellular carcinoma: A retrospective, real-world study conducted in China [J].
Wang, Dong-Xu ;
Yang, Xu ;
Lin, Jian-Zhen ;
Bai, Yi ;
Long, Jun-Yu ;
Yang, Xiao-Bo ;
Seery, Samuel ;
Zhao, Hai-Tao .
WORLD JOURNAL OF GASTROENTEROLOGY, 2020, 26 (30) :4465-4478
[117]   Distribution and Activity of Lenvatinib in Brain Tumor Models of Human Anaplastic Thyroid Cancer Cells in Severe Combined Immune Deficient Mice [J].
Wang, Rong ;
Yamada, Tadaaki ;
Arai, Sachiko ;
Fukuda, Koji ;
Taniguchi, Hirokazu ;
Tanimoto, Azusa ;
Nishiyama, Akihiro ;
Takeuchi, Shinji ;
Yamashita, Kaname ;
Ohtsubo, Koshiro ;
Matsui, Junji ;
Onoda, Naoyoshi ;
Hirata, Eishu ;
Taira, Shu ;
Yano, Seiji .
MOLECULAR CANCER THERAPEUTICS, 2019, 18 (05) :947-956
[118]   Variable Intra-Tumor Genomic Heterogeneity of Multiple Lesions in Patients With Hepatocellular Carcinoma [J].
Xue, Ruidong ;
Li, Ruoyan ;
Guo, Hua ;
Guo, Lin ;
Su, Zhe ;
Ni, Xiaohui ;
Qi, Lisha ;
Zhang, Ti ;
Li, Qiang ;
Zhang, Zemin ;
Xie, Xiaoliang Sunney ;
Bai, Fan ;
Zhang, Ning .
GASTROENTEROLOGY, 2016, 150 (04) :998-1008
[119]   Lenvatinib, an angiogenesis inhibitor targeting VEGFR/FGFR, shows broad antitumor activity in human tumor xenograft models associated with microvessel density and pericyte coverage [J].
Yamamoto, Yuji ;
Matsui, Junji ;
Matsushima, Tomohiro ;
Obaishi, Hiroshi ;
Miyazaki, Kazuki ;
Nakamura, Katsuji ;
Tohyama, Osamu ;
Semba, Taro ;
Yamaguchi, Atsumi ;
Hoshi, Sachi Suzuki ;
Mimura, Fusayo ;
Haneda, Toru ;
Fukuda, Yoshio ;
Kamata, Jun-ichi ;
Takahashi, Keiko ;
Matsukura, Masayuki ;
Wakabayashi, Toshiaki ;
Asada, Makoto ;
Nomoto, Ken-ichi ;
Watanabe, Tatsuo ;
Dezso, Zoltan ;
Yoshimatsu, Kentaro ;
Funahashi, Yasuhiro ;
Tsuruoka, Akihiko .
VASCULAR CELL, 2014, 6
[120]   REFLECT-a phase 3 trial comparing efficacy and safety of lenvatinib to sorafenib for the treatment of unresectable hepatocellular carcinoma: an analysis of Japanese subset [J].
Yamashita, Tatsuya ;
Kudo, Masatoshi ;
Ikeda, Kenji ;
Izumi, Namiki ;
Tateishi, Ryosuke ;
Ikeda, Masafumi ;
Aikata, Hiroshi ;
Kawaguchi, Yasunori ;
Wada, Yoshiyuki ;
Numata, Kazushi ;
Inaba, Yoshitaka ;
Kuromatsu, Ryoko ;
Kobayashi, Masahiro ;
Okusaka, Takuji ;
Tamai, Toshiyuki ;
Kitamura, Chifumi ;
Saito, Kenichi ;
Haruna, Katsuya ;
Okita, Kiwamu ;
Kumada, Hiromitsu .
JOURNAL OF GASTROENTEROLOGY, 2020, 55 (01) :113-122