Efficacy and safety of sorafenib in patients with alcohol-related hepatocellular carcinoma: A sub-analysis from the SHARP trial

15591 Background: The majority of patients with HCC present with advanced disease and are therefore not suitable for curative treatment. The only systemic therapy currently approved for HCC is sorafenib, a multi-kinase inhibitor. Approval of sorafenib by the FDA and EMEA for the treatment of HCC followed results from the phase III Sorafenib HCC Assessment Randomized Protocol (SHARP) trial, which demonstrated that sorafenib 400mg b.i.d. improves overall survival (OS) versus placebo in advanced HCC. The etiological factors most commonly linked to HCC are infection with either hepatitis B virus (HBV) or hepatitis C virus (HCV), and alcohol abuse. Here we report a subgroup analysis of SHARP assessing safety and efficacy of sorafenib in patients with alcohol-related advanced HCC. Methods: In SHARP, 602 patients with advanced, unresectable HCC were randomized to sorafenib 400mg b.i.d. or placebo. In this subanalysis, OS and time to progression (TTP) were evaluated for patients with alcohol-related HCC. Events were independently assessed. Results: In the intent-to-treat population, the number of patients with alcohol as etiology of the underlying liver disease was 79 in the sorafenib group and 80 in the placebo group. Median OS for sorafenib vs placebo was 10.32 vs 7.99 months (HR: 0.76; 95% CI: 0.50, 1.16) and TTP was 5.52 vs 3.94 months (HR: 0.64; 95% CI: 0.40, 1.03). The proportion of patients who had drug-related, treatment-emergent adverse events was 80.8% in the sorafenib group vs 53.8% in the placebo group. The most common drug-related adverse events in the sorafenib group were diarrhea (47.4%), fatigue (20.5%) and hand-foot skin reaction (20.5%); in the placebo group these adverse events occurred at rates of 10%, 12.5% and 6.3%, respectively. Conclusions: This subanalysis included a relatively small number of patients and, therefore, the data must be interpreted with caution. However, the results from patients with alcohol-related advanced HCC suggest a trend of improved OS and TTP in favor of sorafenib and are consistent with the overall results in the SHARP study population, supporting the use of sorafenib as a valid treatment option for a wide range of patients with HCC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer Bayer, Biocompatibles, Bristol-Myers Squibb AstraZeneca, Eisai, MDS Nordion, sanofi-aventis Bayer, Biocompatibles, Bracco Bayer