Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma and vascular invasion or extrahepatic spread: A subanalysis from the SHARP trial

4584 Background: Liver cancer is the third leading cause of cancer death globally, with most deaths occurring within one year of diagnosis. The multi-kinase inhibitor sorafenib became the first treatment approved by the FDA and EMEA for the treatment of HCC based on data from the phase III Sorafenib HCC Assessment Randomized Protocol (SHARP) trial, which demonstrated that sorafenib 400mg bid increased overall survival (OS) vs placebo in patients with advanced HCC. The influence of risk factors such as macroscopic vascular invasion (MVI) and/or extrahepatic spread (EHS), on the safety and efficacy of sorafenib has not previously been reported. Here we compare sorafenib versus placebo in patients with and without MVI and/or EHS. Methods: Patients with advanced, measurable HCC, Eastern Cooperative Oncology Group performance status (ECOG PS) 0–2 and Child-Pugh status A received either sorafenib (400mg bid) or placebo. Endpoints included OS, time to progression (TTP; based on independent tumor assessment), and safety. Presence of MVI was determined through radiological assessment. Results: In this analysis, 421 patients had MVI and/or EHS (sorafenib=209, placebo=212) and 181 (sorafenib=90, placebo=91) did not. For patients with MVI and/or EHS (sorafenib vs placebo), OS was 8.9 vs 6.7 months (HR: 0.77; 95% CI: 0.60, 0.99) and TTP was 4.1 vs 2.7 months (HR: 0.64; 95% CI: 0.48, 0.84). For patients without MVI and/or EHS, OS was 14.5 vs 10.2 months (HR: 0.52; 95% CI: 0.32, 0.85) and TTP was 9.6 vs 4.3 months (HR: 0.40; 95% CI: 0.23, 0.70). The most common grade 3–4 drug-related, treatment-emergent adverse events (AEs) in the sorafenib arm for patients with vs those without MVI and/or EHS were: diarrhea (5.3 vs 15.7%), hand-foot skin reaction (6.7 vs 10.1%) and fatigue (4.8 vs 1.1%). Conclusions: Sorafenib prolonged OS and TTP in patients with advanced HCC irrespective of presence or absence of MVI and/or EHS; furthermore, sorafenib was well tolerated and AEs were manageable. These data are consistent with those in the overall SHARP population and confirm that the survival benefit achieved with sorafenib extends to a wide range of patients with advanced HCC, including those with MVI and/or EHS. 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