TY - JOUR
T1 - Randomised, multicentre prospective trial of transarterial chemoembolisation (TACE) plus sorafenib as compared with TACE alone in patients with hepatocellular carcinoma
T2 - TACTICS trial
AU - Kudo, Masatoshi
AU - Ueshima, Kazuomi
AU - Ikeda, Masafumi
AU - Torimura, Takuji
AU - Tanabe, Nobukazu
AU - Aikata, Hiroshi
AU - Izumi, Namiki
AU - Yamasaki, Takahiro
AU - Nojiri, Shunsuke
AU - Hino, Keisuke
AU - Tsumura, Hidetaka
AU - Kuzuya, Teiji
AU - Isoda, Norio
AU - Yasui, Kohichiroh
AU - Aino, Hajime
AU - Ido, Akio
AU - Kawabe, Naoto
AU - Nakao, Kazuhiko
AU - Wada, Yoshiyuki
AU - Yokosuka, Osamu
AU - Yoshimura, Kenichi
AU - Okusaka, Takuji
AU - Furuse, Junji
AU - Kokudo, Norihiro
AU - Okita, Kiwamu
AU - Johnson, Philip James
AU - Arai, Yasuaki
N1 - Funding Information:
1Department of gastroenterology and hepatology, Kindai University Faculty of Medicine, Osaka-sayama, Japan 2Department of hepatobiliary and Pancreatic Oncology, national cancer center hospital east, Kashiwa, Japan 3Department of gastroenterology and hepatology, Kurume University school of Medicine, Kurume, Japan 4Department of gastroenterology, national hospital Organisation sendai Medical center, sendai, Japan 5Department of gastroenterology and Metabolism, hiroshima University, hiroshima, Japan 6Department of gastroenterology, Musashino red cross hospital, Tokyo, Japan 7Department of gastroenterology and hepatology, Yamaguchi University graduate school of Medicine, Ube-Yamaguchi, Japan 8Department of gastroenterology and Metabolism, nagoya city University graduate school of Medical sciences, nagoya, Japan 9Department of hepatology and Pancreatology, Kawasaki Medical school, Kurashiki, Japan 10Department of gastroenterology and hepatology, hyogo cancer center, akashi, Japan 11Department of gastroenterology and hepatology, nagoya University graduate school of Medicine, nagoya, Japan 12Department of Medicine, Division of gastroenterology, Jichi Medical University, shimotsuke, Japan 13Department of gastroenterology and hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan 14Division of gastroenterology, Department of Medicine, social insurance Tagawa hospital, Tagawa, Japan 15Department of gastroenterology and hepatology, Kagoshima University graduate school of Medical and Dental sciences, Kagoshima, Japan 16Department of liver, Biliary Tract and Pancreas Diseases, Fujita health University school of Medicine, aichi, Japan 17Department of gastroenterology and hepatology, nagasaki University graduate school of Biomedical sciences, nagasaki, Japan 18Department of hepato-Biliary-Pancreatic surgery, clinical research institute, national hospital Organization Kyushu Medical center, Fukuoka, Japan 19Department of gastroenterology, school of Medicine, chiba University, chiba, Japan 20center for integrated Medical research, hiroshima University, hiroshima, Japan 21Department of hepatobiliary and Pancreatic Oncology, national cancer center hospital, Tokyo, Japan 22Department of Medical Oncology, Kyorin University Faculty of Medicine, Mitaka, Japan 23Department of surgery, national center for global health and Medicine, Tokyo, Japan 24Deapartment of Medicine, shunan Memorial hospital, Kudamatsu, Yamaguchi, Japan 25Department of Molecular and clinical cancer Medicine, University of liverpool, liverpool, UK 26Department of Diagnostic radiology, national cancer center hospital, Tokyo, Japan Acknowledgements We thank the patients, their families, the investigators, the site staff and the teams who participated in this study. This study was supported by Japan liver Oncology group with funding from Bayer Yakuhin, ltd., Japan, under a research contract.
Funding Information:
Funding This study was supported by the Japan liver Oncology group with funding from Bayer Yakuhin, ltd., Japan, under a research contract.
Funding Information:
Competing interests KM: honoraria from Bayer, eisai, MsD, ajinomoto. consulting or advisory role for Kowa, MsD, BMs, Bayer, chugai, Taiho. research funding from chugai, Otuka, Takeda, Taiho, sumitomo Dainippon, Daiichi sankyo, MsD, eisai, Bayer, abbvie. iM: honoraria from novartis Pharma, Bayer Yakuhin, Bristol-Myers squibb, abbott Japan, eisai, Taiho Pharmaceutical, eli lilly Japan, Daiichi-sankyo, Yakult, Otsuka Pharmaceutical, nobelpharma, ea Pharma, Teijin Pharma. consulting or advisory role for nano carrier, Bayer Yakuhin, eisai, Kyowa hakko Kirin, novartis Pharma, shire, MsD, Bristol Myers sqiibb, eli lilly Japan, sumitomo Dainippon, Daiichi-sankyo, Teijin Pharma, Takara Bio. research funding from Bayer Yakuhin, Kyowa hakko Kirin, Yakult, Taiho Pharmaceutical, eli lilly Japan, Ono Pharmaceutical, eisai, astraZeneca, Zeria Pharmaceutical, chugai, Bristol Myers sqiibb, Merck serono, Kowa, nano carrier, aslan, Daiichi-sankyo., sumitomo Dainippon, novartis Pharma, Baxalta, Boehringer ingelheim, Takara Bio. Board membership: aslan, chugai. in: honoraria from Bayer, gilead, abbvie, Otuka. in: research funding from abbvie gK. hK: honoraria from MsD, abbvie, Bristrol-Myers squibb, Dainippon sumitomo and Otsuka, research funding from gilead, Bristrol-Myers squibb, MsD. ia: honoraria from abbVie gK, Bristol Myers squibb, gilead, eisai. research funding from abbVie gK, Otsuka, MsD, chugai, eisai, astellas, Takeda. Kn: research funding from abbvie gK.nakao K: honoraria from gilead. YO: research funding from astraZeneca, asteras, ajinomoto, asahiKasei-Kurare Medical, Bayer Yakuhin, Bristol Myers sqiibb, chugai, Daiichi-sankyo, eisai, Kyowa hakko Kirin, Kowa, nihon Kayaku, MsD, Otsuka, Ono, Taiho, Tanabe-Mitsubishi, Takeda, Torii, Tsumura, Zeria. YK: honoraria from chugai, eli lilly, Taiho, nippon shinyaku. OT: honoraria from novartis, Taiho, eli lilly, Dainippon sumitomo, Bayer, Yakult, FUJiFilM, astraZeneca, Ono Pharmaceutical, ea Pharma, nippon chemiphar, celgene, chugai, Bristol Myers, eisai, Pfizer, Teijin, Daiichi sankyo, MsD, shire, abbVie, Takeda. consulting or advisory role for eli lilly, Dainippon sumitomo, Taiho, Zeria Pharmaceutical, Daiichi sankyo, Bristol Myers. research Funding from eli lilly, eisai, novartis, Yakult honsha, Taiho, Kowa, Kyowa hakko Kirin, Merck serono, Ono Pharmaceutical, Bayer, Pfizer Japan, astraZeneca, Dainippon sumitomo, chugai, Bristol Myers, Zeria Pharmaceutical. Kn: honoraria from eisai. aY: royalties from sumitomo Bakelite. research funding from canon Medical systems, Taiho Pharmaceutical, eisai. honoraria from Merit Medical systems., Fuji Pharma, Terumo international systems, nippon Kayaku, canon Medical systems, Bristol Meyer squibb, sumitomo Bakelite, Bayer Pharmaceuticals, Boston scientific Japan, Taiho Pharmaceutical, guerbet Japan, guerbet asia Pacific.
Publisher Copyright:
© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - Objective This trial compared the efficacy and safety of transarterial chemoembolisation (TACE) plus sorafenib with TACE alone using a newly established TACE-specific endpoint and pre-treatment of sorafenib before initial TACE. Design Patients with unresectable hepatocellular carcinoma (HCC) were randomised to TACE plus sorafenib (n=80) or TACE alone (n=76). Patients in the combination group received sorafenib 400 mg once daily for 2-3 weeks before TACE, followed by 800 mg once daily during on-demand conventional TACE sessions until time to untreatable (unTACEable) progression (TTUP), defined as untreatable tumour progression, transient deterioration to Child-Pugh C or appearance of vascular invasion/extrahepatic spread. Co-primary endpoints were progression-free survival (PFS), which is not a conventional one but defined as TTUP, or time to any cause of death plus overall survival (OS). Multiplicity was adjusted by gatekeeping hierarchical testing. Results Median PFS was significantly longer in the TACE plus sorafenib than in the TACE alone group (25.2 vs 13.5 months; p=0.006). OS was not analysed because only 73.6% of OS events were reached. Median TTUP (26.7 vs 20.6 months; p=0.02) was also significantly longer in the TACE plus sorafenib group. OS at 1 year and 2 years in TACE plus sorafenib group and TACE alone group were 96.2% and 82.7% and 77.2% and 64.6%, respectively. There were no unexpected toxicities. Conclusion TACE plus sorafenib significantly improved PFS over TACE alone in patients with unresectable HCC. Adverse events were consistent with those of previous TACE combination trials. Trial registration number NCT01217034.
AB - Objective This trial compared the efficacy and safety of transarterial chemoembolisation (TACE) plus sorafenib with TACE alone using a newly established TACE-specific endpoint and pre-treatment of sorafenib before initial TACE. Design Patients with unresectable hepatocellular carcinoma (HCC) were randomised to TACE plus sorafenib (n=80) or TACE alone (n=76). Patients in the combination group received sorafenib 400 mg once daily for 2-3 weeks before TACE, followed by 800 mg once daily during on-demand conventional TACE sessions until time to untreatable (unTACEable) progression (TTUP), defined as untreatable tumour progression, transient deterioration to Child-Pugh C or appearance of vascular invasion/extrahepatic spread. Co-primary endpoints were progression-free survival (PFS), which is not a conventional one but defined as TTUP, or time to any cause of death plus overall survival (OS). Multiplicity was adjusted by gatekeeping hierarchical testing. Results Median PFS was significantly longer in the TACE plus sorafenib than in the TACE alone group (25.2 vs 13.5 months; p=0.006). OS was not analysed because only 73.6% of OS events were reached. Median TTUP (26.7 vs 20.6 months; p=0.02) was also significantly longer in the TACE plus sorafenib group. OS at 1 year and 2 years in TACE plus sorafenib group and TACE alone group were 96.2% and 82.7% and 77.2% and 64.6%, respectively. There were no unexpected toxicities. Conclusion TACE plus sorafenib significantly improved PFS over TACE alone in patients with unresectable HCC. Adverse events were consistent with those of previous TACE combination trials. Trial registration number NCT01217034.
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U2 - 10.1136/gutjnl-2019-318934
DO - 10.1136/gutjnl-2019-318934
M3 - Article
C2 - 31801872
AN - SCOPUS:85076181498
VL - 69
SP - 1492
EP - 1501
JO - Gut
JF - Gut
SN - 0017-5749
IS - 8
ER -