Which questions remain unanswered following the successful development of sorafenib in hepatocellular carcinoma?

Investigation of the effects of various antiangiogenic agents in the therapy of solid tumors has been a dominant theme in oncology for the past decade. Hepatocellular carcinoma has joined the short list of tumor types for which single-agent antiangiogenic therapy has shown clear clinical benefit. Here we discuss the findings of a multicenter, phase III trial by Llovet et al., which compared overall survival, time to symptomatic progression, and time to radiologic progression in 602 patients with hepatocellular carcinoma who received either sorafenib (n= 299) or placebo (n = 303). This study showed that patients treated with sorafenib had approximately 3 months longer overall survival and time to radiologic progression compared with patients who received placebo. For optimal clinical application, elucidation of the tumor-specific and patient-specific factors that identify the subpopulation of patients with hepatocellular carcinoma who will derive the greatest benefit from antiangiogenic therapies such as sorafenib is of critical importance.