P-0073 GIDEON (Global Investigation of Therapeutic Decisions in HCC and of its Treatment eith Sorafenib): European Interim Safety and Dosing Subanalysis

Abstract

IntroductionGIDEON (Global Investigation Of Therapeutic Decisions In Hepatocellular Carcinoma (HCC) And Of Its Treatment With Sorafenib) is an ongoing, global, prospective, non-interventional study of patients with HCC eligible for and receiving sorafenib under real-life practice conditions. It aims to assess safety and efficacy of sorafenib in different settings and patient subgroups where data are limited. Findings from the second interim analysis (1571 patients treated for ≥4 months) have been reported. Here we report details of AEs in the European subset. MethodsPatient demographics, medical, disease and treatment history are recorded at enrolment; sorafenib dose, performance status, liver function, AEs and efficacy are recorded at follow-up. Results588 of the 1571 patients were treated in Europe: 59.4% aged ≥65 years, ECOG performance status (PS) 0/1, 45.9/38.9%, and BCLC stage A/B/C/D, 9.0/24.3/52.9/4.9%. Treating physicians’ predominant specialty was hepatology/gastroenterology (56.5% of patients) and medical oncology (32.1%). Most patients (80.6%) were started on sorafenib 800mg daily. Sorafenib dose was modified for 40.8% of patients; 29.8% due to AEs. The dose was increased in 13.8% of patients and decreased in 33.7%. Treatment was interrupted in 20.1% of patients; 16.2% due to AEs. Median treatment duration was 14.3 weeks. Median daily dose was 746mg. A total of 84.5% of patients experienced a treatment-emergent AE. The overall incidence was similar in patients aged <65 or ≥65 years, although the incidence of grade 3/4 AEs was higher in the ≥65 age group; 24.7 vs. 34.7%. The proportion of AEs occurring in the 400mg group was numerically higher than in the 800mg group (92.3% vs. 84.4%), including the grade 3/4 AE subgroup; 35.1% and 30.6% respectively. Incidence appeared lower in BCLC-A patients at start of therapy (66%) vs BCLC B–D (87.4–89.7%). The most frequent AEs were diarrhoea (31.8%; 5.3% Grade ≥3), fatigue (28.2%, 10.4% Grade ≥3), hand-foot skin reaction (HFSR; 18.2%; 4.9% Grade 3). The most common serious AEs were liver dysfunction (8%), encephalopathy (3.4%), fatigue (2.2%), and ascites (2.4%). Most AEs occurred within the first 30 days of treatment. A similar number of drug-related serious AEs were experienced regardless of initial dose. 30.3% of patients discontinued sorafenib due to AEs. Fewer patients started on 800mg daily (29.3%) discontinued treatment vs those started on 400mg (40.7%). AEs leading to permanent discontinuation seemed less frequent in patients treated by medical oncologists, where 68.3% were Child-Pugh A status, albeit with more advanced malignant disease. Medical oncologists treated a greater proportion of patients with sorafenib 800mg daily than hepatologists/gastroenterologists (88.9% vs. 78.6%). The most frequent AEs leading to permanent discontinuation were liver dysfunction (5.3%), fatigue (4.9%), HFSR (2.0%), ascites (1.9%), diarrhoea (1.9%), anorexia (1.5%), encephalopathy (1.5%), and rash (1.2%). ConclusionThe results did not reveal any unexpected AEs and indicate that the incidence of AEs among patients treated with sorafenib in routine clinical practice appears similar to those treated in randomized clinical trials. Furthermore, these data suggest that a modified dosing strategy did not improve upon the incidence of AEs associated with the standard 800mg daily dose of sorafenib.