Global Investigation of Therapeutic Decisions in Hepatocellular Carcinoma and of its Treatment with Sorafenib (GIDEON) second interim analysis in more than 1,500 patients: Clinical findings in patients with liver dysfunction.

Abstract

4001 Background: GIDEON is an ongoing, global, prospective, noninterventional study of hepatocellular carcinoma (HCC) patients (pts) suitable for systemic therapy and receiving sorafenib (Sor) in real-life practice. Its aim is to evaluate Sor safety and efficacy in diverse settings and pt subgroups where data are limited such as pts with liver dysfunction ie Child-Pugh B (CP-B). Methods: Demographics, medical/disease/treatment history are recorded. At follow-up visits Sor dose, concomitant treatment, liver function, adverse events (AEs) and efficacy are recorded. From Jan 2009 to Dec 2010, 2,770 pts were enrolled in 37 countries. Per protocol, the 2nd interim analysis (IA) was planned when ~1,500 treated pts were followed ≥4 mos. Results: 1,586 pts comprise the safety population; CP-A, 965 (61%); CP- B, 368 (23%). Sor median daily dose was higher in the CP-B group, but median duration of therapy was shorter (Table). Treatment-emergent drug-related AE rates were similar in both groups, but a greater percentage of CP-B pts discontinued Sor due to AEs. Deaths during treatment up to 30 days of last Sor dose were greater in the CP-B group (34%) than in the CP-A group (15%). In the ITT population (1614 pts), preliminary median overall survival (OS) was 10.5 mos in the CP-A pts (n=982) and 5 mos in the CP-B pts (n=373). Conclusions: These preliminary second IA results indicate that the Sor safety profile is generally similar in the CP-B and CP-A pts. The shorter median OS in the CP-B pts most likely reflects the poorer prognosis and natural history of liver disease in this patient population. N = 1,586 CP-A n = 965 (61%) CP-B n = 368 (23%) 800 mg starting dose (n [%]) 738 (76) 261 (71) Daily dose (median, mg)* 684.5 721.0 No. dose reductions (n [%]) 353 (37) 99 (27) Treatment duration (median, wks)* 13.7 8.5 Treatment-emergent AEs (n [%]) All Drug-related All Drug-related All grades 768 (80) 632 (66) 322 (88) 227 (62) Grade 3 241 (25) 211 (22) 94 (26) 67 (18) Grade 4 37 (4) 16 (2) 20 (5) 9 (2) Serious, all grades (n (%)) 273 (28) 75 (8) 198 (54) 53 (14) Sor discontinued due to AEs (n [%]) 217 (23) 139 (38) * Missing data not tabulated.