Second interim analysis of the Global Investigation of Therapeutic Decisions in Unresectable HCC and of Its Treatment with Sorafenib (GIDEON): Sorafenib dosing and safety in U.S. patients.

Abstract

302 Background: Sorafenib (SOR) is the first systemic therapy to improve survival in patients (pts) with advanced hepatocellular carcinoma (HCC). GIDEON is a global, prospective, noninterventional study to evaluate SOR safety in pts with unresectable HCC in real-life practice. We present results from the second interim analysis, describing SOR dosing in US pts. Methods: From Jan 2009 – Nov 2010, 326 pts were enrolled in 92 US centers and followed ≥4 months, with 313 pts evaluable for safety. Demographics, initial dose, treatment duration (TD), dose modifications (mods), treatment interruptions (TIs), and adverse events (AEs) were analyzed in pts with complete data available. Results: Initial SOR dose was 400 mg/d in 106 pts (34%) and 800 mg/d in 177 pts (57%). Thirty (10%) pts received alternate doses or had incomplete data. Most pts were male (400 mg/d: 75%; 800 mg/d: 80%). Age distribution was similar between groups (400 mg/d: 59% <65 yr and 41% >65 yr; 800 mg/d: 64% <65 yr and 36% >65 yr). In 400 mg/d vs 800 mg/d groups respectively, ECOG PS was 0/1/2 in 19%/49%/16% vs 34%/35%/12%, and Child-Pugh (CP) status was A/B/C in 32%/35%/7% (26% unevaluable) vs 42%/29%/6% (21% unevaluable). Median TD was 9.8 wks (<4 wks in 22%, >4-12 wks in 40%, and >12 wks in 39%) in the 400 mg/d group and 13.2 wks (<4 wks in 17%, >4-12 wks in 29%, and >12 wks in 53%) in the 800 mg/d group. Dose mods and TIs occurred in 49% (37% due to AE) and 35%, and 57% (36% due to AE) and 38% of 400 mg/d vs 800 mg/d pts, respectively. See table for safety data. Conclusions: While statistical comparisons were not made, PS or CP status may impact initial SOR dose selection. Other baseline characteristics did not affect this decision. Frequencies of dose mods, TIs, and AEs were similar between dosing groups. Limitations of an observational study must be considered. Clinical judgment remains important in choosing initial SOR dose. [Table: see text]