Randomised, multicentre prospective trial of transarterial chemoembolisation (TACE) plus sorafenib as compared with TACE alone in patients with hepatocellular carcinoma: TACTICS trial.

Abstract

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.

• Authors: Masatoshi Kudo, Kazuomi Ueshima, Masafumi Ikeda, Takuji Torimura, Nobukazu Tanabe, Hiroshi Aikata, Namiki Izumi, Takahiro Yamasaki, Shunsuke Nojiri, Keisuke Hino, Hidetaka Tsumura, Teiji Kuzuya, Norio Isoda, Kohichiroh Yasui, Hajime Aino, Akio Ido, Naoto Kawabe, Kazuhiko Nakao, Yoshiyuki Wada, Osamu Yokosuka, Kenichi Yoshimura, Takuji Okusaka, Junji Furuse, Norihiro Kokudo, Kiwamu Okita, Philip James Johnson, Yasuaki Arai, TACTICS study group
• Journal: Gut (Gut) Vol. 69 Issue 8 Pg. 1492-1501 (08 2020) ISSN: 1468-3288 [Electronic] England
• PMID: 31801872 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• 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.

Chemical References

• Antineoplastic Agents
• Sorafenib

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (adverse effects, therapeutic use)
• Carcinoma, Hepatocellular (therapy)
• Chemoembolization, Therapeutic (adverse effects)
• Combined Modality Therapy
• Disease Progression
• Female
• Humans
• Liver Neoplasms (therapy)
• Male
• Middle Aged
• Progression-Free Survival
• Prospective Studies
• Sorafenib (adverse effects, therapeutic use)
• Survival Rate