Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Dec 18, 2016; 8(35): 1541-1546
Published online Dec 18, 2016. doi: 10.4254/wjh.v8.i35.1541
How to assess the efficacy or failure of targeted therapy: Deciding when to stop sorafenib in hepatocellular carcinoma
Jean-Luc Raoul, Xavier Adhoute, Marine Gilabert, Julien Edeline
Jean-Luc Raoul, Marine Gilabert, Department of Medical Oncology, Paoli-Calmettes Institute, 13273 Marseille, France
Xavier Adhoute, Department of Hepatology, Hopital Saint-Joseph, 13008 Marseille, France
Julien Edeline, Department of Medical Oncology, Centre E Marquis, Bd de la Bataille Frandres-Dunkerque, 35043 Rennes Cedex, France
Author contributions: Raoul JL, Adhoute X, Gilabert M and Edeline J wrote the paper and approved its content.
Conflict-of-interest statement: Raoul JL has received consultancy fees from Bayer, Taiho, and BTG; Adhoute X has received consultancy fees from Bayer; Gilabert M and Edeline J have no potential conflicts of interest to disclose.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Dr. Jean-Luc Raoul, Professor, Department of Medical Oncology, Paoli-Calmettes Institute, BP 156, 13273 Marseille, France.
Telephone: +33-4-91223679 Fax: +33-4-91223670
Received: March 15, 2016
Peer-review started: March 18, 2016
First decision: April 18, 2016
Revised: September 20, 2016
Accepted: November 1, 2016
Article in press: November 2, 2016
Published online: December 18, 2016

Sorafenib is thus far the only systemic treatment for hepatocellular carcinoma (HCC) based on the results of two randomized controlled trials performed in Western and in Eastern countries, despite a poor response rate (from 2% to 3.3%) following conventional evaluation criteria. It is now recognized that the criteria (European Association of the Study of the Liver criteria, modified response evaluation criteria in solid tumors) based on contrast enhanced techniques (computed tomography scan, magnetic resonance imaging) aimed to assess the evolution of the viable part of the tumor (hypervascularized on arterial phase) are of major interest to determine the efficacy of sorafenib and of most antiangiogenic drugs in patients with HCC. The role of alpha-fetoprotein serum levels remains unclear. In 2016, in accordance with the SHARP and the Asia-Pacific trials, sorafenib must be stopped when tolerance is poor despite dose adaptation or in cases of radiological and symptomatic progression. This approach will be different in cases of available second-line therapy trials. Some recent data (in renal cell carcinoma) revealed that despite progression in patients who received sorafenib, this drug can still decrease tumor progression compared to drug cessation. Then, before deciding to continue sorafenib post-progression or shift to another drug, knowing other parameters of post-progression survival (Child-Pugh class, Barcelona Clinic Liver Cancer, alpha-fetoprotein, post-progression patterns in particular, the development of extrahepatic metastases and of portal vein thrombosis) will be of major importance.

Keywords: Tumor evaluation, Response evaluation criteria in solid tumors, Sorafenib, Hepatocellular carcinoma, Modified response evaluation criteria in solid tumors

Core tip: The response rate of sorafenib in hepatocellular carcinoma is low using standard parameters and is better assessed using new criteria based on tumor vascularization (European Association of the Study of the Liver criteria, modified response evaluation criteria in solid tumors). In case of minor progression, if sorafenib is well tolerated, knowing the predictors of post-progression survival will be of value in deciding whether to continue or stop sorafenib.