Global Investigation Of Therapeutic Decisions Research Articles

Second interim analysis of GIDEON (Global Investigation of Therapeutic Decisions in Unresectable HCC and of Its Treatment with Sorafenib): U.S. versus global perspective on patient and disease characteristics, treatment history, and sorafenib use.

278 Background: GIDEON is a global, prospective, noninterventional study of patients (pts) treated with sorafenib (SOR) for unresectable hepatocellular carcinoma (uHCC). Regions evaluated included US, Europe, Japan, Asia Pacific, and Latin America. Detailed regional data were presented by Kudo et al (ILCA 2011, abstr 0-030). Data from the second US interim analysis are compared to global results. Methods: Eligible pts had uHCC and were treated with SOR. Demographics, disease etiology, treatment history, and SOR dosing were compared in a descriptive, preplanned subgroup analysis. Results: Global and US safety populations comprised 1571 and 313 pts, respectively. In the US, hepatitis B was less common (18% vs 37% global) whereas hepatitis C was more frequent (53% vs 32% global). Alcoholic liver disease etiology was higher in US pts (41% vs 29% global). US pts were diagnosed with later-stage disease, but fewer US pts had documented BCLC and Child-Pugh status. Fewer US pts had an ECOG PS 0 at start of SOR (28% vs 40% global). Rates of prior surgery and locoregional treatment were similar in US (11% and 49%, respectively) and global pts (19% and 55%, respectively). US pts treated with TACE (n = 116) underwent fewer TACE procedures (≥3: 13.8% vs 38.9% global); most (59%) TACE-treated pts in the US received 1 treatment. In US vs global pts, median time from prior surgery to start of SOR was 10 months (range 1-61) vs 14 months (range 1-181) and median time from last TACE to start of SOR was 3.2 months vs 3.1 months. Conclusions: Disease characteristics and treatment patterns for pts with uHCC in the US differ from those in the global population. US pts enrolled in GIDEON (ie, receiving SOR) have differing etiologies of liver disease and have a greater proportion of hepatic dysfunction, likely accounting for worse performance status. [Table: see text]

Worldwide trends in locoregional therapy for hepatocellular carcinoma (HCC): Second interim analysis of the Global Investigation of Therapeutic Decisions in HCC and of Its Treatment with Sorafenib (GIDEON) study.

317 Background: Locoregional treatments (LRTs) are widely used for HCC, with recognized regional variations but no universal standard. GIDEON is a global, prospective, non-interventional study evaluating sorafenib use in HCC patients (pts). The study allows evaluation of global trends in LRTs. Methods: >3000 pts were enrolled in 39 countries (January 2009 to April 2011). Per protocol, the 2nd interim analysis was planned when ~1500 treated pts were followed for ≥4 months. Results: In the safety population analyzed (N=1571), 55% and 46% of pts received prior LRT and transarterial chemoembolization (TACE), respectively. Prior LRTs, including TACE, were more frequent in Asia-Pacific (AP) and Japan than in other regions. In pts who received TACE prior to the initiation of sorafenib therapy, the number of TACE treatments ≥3 was higher in AP and Japan than in other regions. Overall, 76% of pts received conventional TACE, and the most common TACE agent was doxorubicin. Median time from last TACE to initiation of sorafenib therapy was 3.1 months (Table). Worldwide, 8% of pts received TACE, concomitantly with sorafenib. The incidence of sorafenib-related adverse events/serious adverse events was generally similar in pts who did (70%/4%) or did not (64%/9%) receive concomitant TACE. Conclusions: The GIDEON study provides unique insight into the utilization of LRTs worldwide and contributes to better understanding and management of HCC pts. [Table: see text]

6500 ORAL Second Interim Results of the GIDEON (Global Investigation of Therapeutic DEcisions in HCC and of Its Treatment With SorafeNib) Study – Barcelona-Clinic Liver Cancer (BCLC) Stage Subgroup Analysis

6500 ORAL Second Interim Results of the GIDEON (Global Investigation of Therapeutic DEcisions in HCC and of Its Treatment With SorafeNib) Study – Barcelona-Clinic Liver Cancer (BCLC) Stage Subgroup Analysis

Sorafenib treatment and safety profile in Child Pugh B patients characterized in first interim results of GIDEON (global investigation of therapeutic decisions in hepatocellular carcinoma and of its treatment with sorafenib)

Sorafenib treatment and safety profile in Child Pugh B patients characterized in first interim results of GIDEON (global investigation of therapeutic decisions in hepatocellular carcinoma and of its treatment with sorafenib)

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.

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.

Abstract No. 241: Worldwide trends in locoregional therapy for hepatocellular carcinoma (HCC): First interim analysis of the global investigation of therapeutic decisions in HCC and of its treatment with sorafenib (GIDEON) study

Locoregional treatments (LRTs) are widely used for HCC but with recognized regional differences across the world and no universal standard. GIDEON is a global, prospective, non-interventional study designed to assess the impact of sorafenib therapy for patients with HCC. It also allows for the evaluation of global trends in LRTs.

First interim results of the global investigation of therapeutic decisions in hepatocellular carcinoma (HCC) and of its treatment with sorafenib (GIDEON) study: Use of sorafenib (Sor) by oncologists and nononcologists in the management of HCC.

157 Background: GIDEON is an ongoing, global, prospective, non-interventional registry study of patients (pts) with unresectable HCC (uHCC) receiving Sor under real-life practice settings. From January 2009 to September 2010, over 2,200 pts have been enrolled from 32 countries. Per protocol, the first planned interim analysis was triggered when 500 enrolled pts were followed for at least 4 mos; the primary safety and efficacy results were reported in October 2010. A preplanned subset analysis of treatment patterns across MD specialities is reported here. Methods: Demographics, medical, disease and treatment history are recorded at enrolment; Sor dose, concomitant treatments, performance status, liver function are noted at follow-up. Standard efficacy measures and adverse events (AEs) are captured. Preplanned subanalysis by MD specialty was conducted. Results: Of the 141 treating MDs, 69 (49%) were hepatologists/gastroenterologists (Hep/GIs), 55 (39%) were medical oncologists (Oncs) and 17 (12%) were other specialties. Descriptive statistics of differences in pts' HCC stage, Sor treatment and AEs by the main specialties are shown for the 479 pts evaluable for safety (Table). Conclusions: Interim data from the GIDEON study suggests differential use of Sor by MD specialties. It appears that Oncs tend to treat with lower doses of Sor and for a somewhat shorter duration than Hep/GIs. If these data persist, it will be important to explore the reasons for these differences in Sor usage between Oncs and Hep/GIs and potential impact on patient outcomes. [Table: see text] No significant financial relationships to disclose.

Treatment of Intermediate/Advanced Hepatocellular Carcinoma in the Clinic: How Can Outcomes Be Improved?

Hepatocellular carcinoma (HCC) is a complex condition associated with a poor prognosis. Treatment outcomes are affected by multiple variables, including liver function, performance status of the patient, and tumor stage, making a multidisciplinary approach to treatment essential for optimal patient management. Only ∼30% of patients are eligible for curative therapies (surgery or ablation); palliative treatments include transcatheter arterial chemoembolization (TACE) and sorafenib. Treatment choice is guided by staging systems and treatment guidelines, although numerous systems exist and treatment guidelines vary by region. The current standard of care for patients unsuitable for potentially curative therapy is locoregional therapy with TACE. This treatment is associated with survival benefits, but there is no consensus regarding the optimum treatment/retreatment strategy. For patients with more advanced disease or who have failed locoregional therapy, sorafenib is the standard of care. Sorafenib is a targeted agent with proven survival benefits as monotherapy in these patients, and ongoing studies will clarify its role in combination with other agents and in patients with impaired liver function. Although other novel agents and therapeutic approaches are emerging, such as radioembolization and various targeted agents, further suitably designed randomized clinical trials (RCTs) comparing these agents with the standard of care are needed. In addition to RCTs, the collection of real-life data will also be important to allow physicians to make fully informed treatment decisions. The Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib (GIDEON) study is a global, noninterventional study of patients with unresectable HCC receiving sorafenib. The aim of that study is to compile a large robust database to evaluate local, regional, and global factors influencing the management of patients with HCC. It is hoped that findings from the GIDEON study along with phase III RCT data will lead to better outcomes for patients with intermediate-advanced HCC.