Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma according to ECOG performance status: A subanalysis from the SHARP trial

4587 Background: Most patients with HCC present with advanced disease; until recently, there were no proven treatment options in this setting. In late 2007, the FDA and EMEA granted approval of sorafenib, an oral multi-kinase inhibitor, in the treatment of advanced HCC following demonstration of a significant overall survival (OS) benefit in the phase III SHARP trial. SHARP recruited patients with ECOG PS 0–2, but the influence of PS on safety and efficacy of sorafenib has not previously been reported. Here we report a subanalysis of SHARP, analyzing the effect of ECOG PS on outcomes in this trial. Methods: Patients with advanced measurable HCC, ECOG PS 0–2 and no cirrhosis or Child-Pugh status A, received either sorafenib (400mg bid) or placebo. Treatment groups were stratified according to region, ECOG PS, and extrahepatic spread or vascular invasion. Endpoints included OS, time to progression (TTP; based on independent tumor assessment), and safety. Patients were grouped according to ECOG PS 0 or 1–2 for this analysis. Results: A total of 602 patients were eligible, 325 (sorafenib=161, placebo=164) had ECOG PS 0 at baseline and 277 (sorafenib=138, placebo=139) had PS 1–2. Among patients with PS 0, median OS for sorafenib vs placebo was 13.3 vs 8.8 months (HR: 0.68; 95% CI: 0.50, 0.95) and median TTP was 5.5 vs 2.9 months (HR: 0.55; 95% CI: 0.40, 0.77). Among patients with PS 1–2, median OS for sorafenib vs placebo was 8.9 vs 5.6 months (HR: 0.71; 95% CI: 0.52, 0.96) and median TTP was 5.3 vs 2.8 months (HR: 0.61; 95% CI: 0.42, 0.88). There were no notable differences in the adverse event (AE) profile of sorafenib in patients with PS 0 compared with PS 1–2. The incidence rates for grade 3–4 drug-related AEs in the sorafenib arm for patients with PS 0 vs PS 1–2 were: diarrhea (8.8 vs 8.0%), fatigue (2.5 vs 5.1%), hand-foot skin reaction (8.8 vs 6.6%), hypertension (1.9 vs 1.5%) and pain (any event) (3.1 vs 2.9%). Conclusions: Compared with placebo, sorafenib prolonged OS and TTP in patients with advanced HCC irrespective of ECOG PS 0 or 1–2. Treatment was well tolerated. Overall, these data suggest that sorafenib extends survival in HCC patients with ECOG PS 1–2 in addition to PS 0, and further support sorafenib as the new standard of care in this setting. 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 Bayer, Biocompatibles, Bracco Bayer