Phase III study of sorafenib after transarterial chemoembolisation in Japanese and Korean patients with unresectable hepatocellular carcinoma.

Abstract

BACKGROUND:

In Japan and South Korea, transarterial chemoembolisation (TACE) is an important locoregional treatment for patients with unresectable hepatocellular carcinoma (HCC). Sorafenib, a multikinase inhibitor, has been shown effective and safe in patients with advanced HCC. This phase III trial assessed the efficacy and safety of sorafenib in Japanese and Korean patients with unresectable HCC who responded to TACE.

METHODS:

Patients (n=458) with unresectable HCC, Child-Pugh class A cirrhosis and ≥25% tumour necrosis/shrinkage 1-3 months after 1 or 2 TACE sessions were randomised 1:1 to sorafenib 400mg bid or placebo and treated until progression/recurrence or unacceptable toxicity. Primary end-point was time to progression/recurrence (TTP). Secondary end-point was overall survival (OS).

FINDINGS:

Baseline characteristics in the two groups were similar; >50% of patients started sorafenib>9 weeks after TACE. Median TTP in the sorafenib and placebo groups was 5.4 and 3.7 months, respectively (hazard ratio (HR), 0.87; 95% confidence interval (CI), 0.70-1.09; P=0.252). HR (sorafenib/placebo) for OS was 1.06 (95% CI, 0.69-1.64; P=0.790). Median daily dose of sorafenib was 386 mg, with 73% of patients having dose reductions and 91% having dose interruptions. Median administration of sorafenib and placebo was 17.1 and 20.1 weeks, respectively. No unexpected adverse events were observed.

INTERPRETATION:

This trial, conducted prior to the reporting of registrational phase III trials, found that sorafenib did not significantly prolong TTP in patients who responded to TACE. This may have been due to delays in starting sorafenib after TACE and/or low daily sorafenib doses.

• Authors: Masatoshi Kudo, Kazuho Imanaka, Nobuyuki Chida, Kohei Nakachi, Won-Young Tak, Tadatoshi Takayama, Jung-Hwan Yoon, Takeshi Hori, Hiromitsu Kumada, Norio Hayashi, Shuichi Kaneko, Hirohito Tsubouchi, Dong Jin Suh, Junji Furuse, Takuji Okusaka, Katsuaki Tanaka, Osamu Matsui, Michihiko Wada, Iku Yamaguchi, Toshio Ohya, Gerold Meinhardt, Kiwamu Okita
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 47 Issue 14 Pg. 2117-27 (Sep 2011) ISSN: 1879-0852 [Electronic] England
• PMID: 21664811 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Benzenesulfonates
• Phenylurea Compounds
• Pyridines
• Niacinamide
• Sorafenib

Topics

• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Benzenesulfonates (administration & dosage)
• Carcinoma, Hepatocellular (therapy)
• Chemoembolization, Therapeutic (methods)
• Chemotherapy, Adjuvant
• Combined Modality Therapy
• Disease Progression
• Double-Blind Method
• Female
• Humans
• Intention to Treat Analysis
• Japan
• Liver Neoplasms (therapy)
• Male
• Middle Aged
• Niacinamide (analogs & derivatives)
• Phenylurea Compounds
• Pyridines (administration & dosage)
• Republic of Korea
• Sorafenib
• Survival Analysis
• Treatment Outcome