Systemic treatment for advanced hepatocellular carcinoma: the search of new agents to join sorafenib in the effective therapeutic armamentarium.

INTRODUCTION: Hepatocelullar carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Despite the implementation of screening programs for high-risk individuals, a significant proportion of patients present with advanced disease at the moment of diagnosis. AREAS COVERED: In this review we will focus in the current treatment of advanced HCC, the research that has been done in the past few years, the achievements and failures in this setting and future perspectives. EXPERT OPINION: Sorafenib was the first drug that has shown to increase survival in patients with advanced hepatocelullar carcinoma with an adequate safety profile. Recently, regorafenib was reported to improve survival in a second line randomised placebo controlled phase 3 clinical trial, which represents a major breakthrough in this field after many disappointing results coming from several clinical trials. However, still there is an unmet need for an effective and tolerable treatment for patients who progressed and/or have intolerance to sorafenib. The ultimate goal of the research is to provide drugs that improve survival with acceptable adverse events. Understanding of mechanisms of hepatocarcinogesis, individualizing therapy according to the profile of the population and finding reliable surrogate end-points for survival for early phase trials with new agents should improve the likelihood of achieving these objectives.