The Sorafenib for Hepatocellular Carcinoma (HCC) in Adjuvant Setting: The End of the Story was Already Written?

Abstract

Although early diagnosis of hepatocellular carcinoma (HCC) can improve survival, the outcome after treatment with curative intent can be hampered by early recurrence (30%-40%) or secondary primary tumor (60-70%) [1]. Recurrence after resection may reach 50% and 80% of cases at 2 and 5 years respectively [2], with a 5-year survival of 50% [3] even in the case of early stage without portal venous invasion or satellite nodules [4]. Recurrences compromising dramatically shorten overall survival [5], preventing or delaying relaying relapse after curative treatment has become a major challenge. Recently, Bruix et al. [6] communicated, on behalf of all investigators, the results of the STORM (NCT00692770) trial at the ASCO (American Society of Clinical Oncology) 2014 meeting. This international randomized placebo-controlled phase III trial investigated for 4-years adjuvant sorafenib or placebo in patients with HCC treated either by resection or local ablation. The hypothesis of the study was that sorafenib could reduce tumor recurrence and therefore improve the overall survival. The primary and secondary endpoints of the trial were the recurrence-free survival and overall survival and safety, respectively [6]. The trial enrolled the largest cohort of patients with HCC treated in this setting. Overall, 1,114 patients were equitably randomized to take either sorafenib or placebo. The study did not met its primary and secondary endpoints since no differences were observed regarding recurrence-free survival (33.4 vs 33.8 months; HR=0.94; 95% CI: 0.78-1.13, p=0.26), time to recurrence (38.6 vs 35.8 months; HR=0.89, 95% CI: 0.73-1.08) and overall survival (not reached vs not reached, HR=0.99, 95% CI: 0.76-1.30, p=0.48). In this trial, a higher rate of sorafenib discontinuation due to drug-adverse events was observed compared to placebo (24% vs 7%) [6].