First interim analysis of the GIDEON (Global Investigation of therapeutic decisions in hepatocellular carcinoma and of its treatment with sorafeNib) non-interventional study.

AIMS: Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib (GIDEON), a global, non-interventional, surveillance study, aims to evaluate the safety of sorafenib in all patients with unresectable hepatocellular carcinoma (uHCC) under real-life practice conditions, particularly Child-Pugh B patients, who were not well represented in clinical trials. METHODS: Treatment decisions are determined by each physician according to local prescribing guidelines and clinical practice. Patients with uHCC who are candidates for systemic therapy, and for whom a decision has been made to treat with sorafenib, are eligible for inclusion. Demographic data and medical and disease history are recorded at entry. Sorafenib dosing and adverse events (AEs) are collected throughout the study. RESULTS: From January 2009 to April 2011, >3000 patients from 39 countries were enrolled. The prespecified first interim analysis was conducted when the initial approximately 500 treated patients had been followed up for ≥4 months; 479 were valid for safety evaluation. Preplanned subgroup analyses indicate differences in patient characteristics, disease aetiology and previous treatments by region. Variation in sorafenib dosing by specialty are also observed; Child-Pugh status did not appear to influence the starting dose of sorafenib. The type and incidence of AEs was consistent with findings from previous clinical studies. AE profiles were comparable between Child-Pugh subgroups. DISCUSSION: The GIDEON study is generating a large, robust database from a broad population of patients with uHCC. First interim analyses have shown global and regional differences in patient characteristics, disease aetiology and practice patterns. Subsequent planned analyses will allow further evaluation of early trends.

Efficacy and safety of sorafenib in patients with advanced renal cell carcinoma with and without prior cytokine therapy, a subanalysis of TARGET.

Before the development of targeted therapies, administration of cytokines (e.g., interleukin-2, interferon-alpha) was the primary systemic treatment option for advanced renal cell carcinoma. Sorafenib, an oral targeted, multikinase inhibitor, significantly prolonged progression-free survival and overall survival in the Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET), a large (N = 903) phase III, double-blind, randomised, placebo-controlled study of patients with advanced renal cell carcinoma resistant to standard therapy. This analysis of a patient subgroup from TARGET evaluated the safety and efficacy of sorafenib in patients who had received prior cytokine therapy (sorafenib: n = 374; placebo: n = 368) and in patients who were cytokine-naïve (sorafenib: n = 77; placebo: n = 84). Progression-free survival was significantly prolonged with sorafenib therapy compared with placebo among patients with and without prior cytokine therapy (respectively 5.5 vs. 2.7 months; hazard ratio, 0.54; 95% confidence interval, 0.45-0.64 and 5.8 vs. 2.8 months; hazard ratio, 0.48; 95% confidence interval, 0.32-0.73). Clinical benefit rates for sorafenib-treated patients compared with placebo patients were also higher (cytokine-treated: 83 vs. 54.3%; cytokine-naïve: 85.7 vs. 56.0%). Sorafenib was well tolerated in both subgroups (grade 3/4: 20 and 22%, respectively). Sorafenib demonstrated a consistent, significant clinical benefit against advanced renal cell carcinoma, with a twofold improvement in progression-free survival and disease control rate, with similar toxicities in patients with or without prior cytokine treatment.

Phase I study to determine the safety and pharmacokinetics of the novel Raf kinase and VEGFR inhibitor BAY 43-9006, administered for 28 days on/7 days off in patients with advanced, refractory solid tumors.

BACKGROUND: BAY 43--9006, an oral multi-kinase inhibitor, targets serine-threonine kinases and receptor tyrosine kinases, and affects the tumor and vasculature in preclinical models. Based on its pharmacologic effect, it may be a useful cancer treatment. This study determined the maximum tolerated dose (MTD) of BAY 43-9006 in 42 patients with advanced, refractory metastatic or recurrent solid tumors. Dose-limiting toxicities (DLTs), safety, pharmacokinetics and tumor response were also evaluated. PATIENTS AND METHODS: In this open-label, phase I, dose-escalation study, BAY 43--9,006 was administered orally in repeated cycles of 35 days (28 days on/7 days off). Eight doses were investigated: from 50 mg every fourth day to 600 mg twice daily. Treatment continued until unacceptable toxicity, tumor progression or death. RESULTS: The MTD was 400 mg twice daily. BAY 43-9006 was well tolerated, with mild to moderate toxicities; only six patients discontinued study therapy due to adverse events. DLTs consisted of hand-foot skin reaction in three of seven patients receiving 600 mg twice daily. Stable disease was achieved in 22% of patients; median duration of stable disease was 7.2 months. Consistent with its observed half-life of approximately 27 h, BAY 43-9, 006 accumulated on multiple dosing. Increases in exposure were less than proportional to the increases in dose. CONCLUSIONS: Results indicate that further clinical investigation of BAY 43--9006 is warranted, and suggest it could be a promising future therapy for patients with cancer.