Therapeutic Decisions In Hepatocellular Carcinoma Research Articles

Safety assessment of sorafenib in Chinese patients with unresectable hepatocellular carcinoma: subgroup analysis of the GIDEON study

BackgroundThis study aimed to investigate the safety of sorafenib for the treatment of unresectable hepatocellular carcinoma in Chinese patients.MethodsA subgroup of 345 Chinese patients from the international database of the Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib (GIDEON) study was included in this analysis. Safety assessment measures were adverse events (AEs) and serious adverse events (SAEs) graded using the National Cancer Institute Common Terminology Criteria version 3.0.ResultsOf 331 evaluable patients, 98% started sorafenib at 800 mg/day. The median treatment duration was 22 weeks (range, 0.1–116 weeks), and median overall survival (OS) was 322 days (10.7 months). Approximately 50% of patients had at least one adverse event, and 6% had grade 3–4 adverse events. Drug-related adverse events were experienced by 29% of patients, and 3.6% had grade 3–4 drug-related adverse events. Overall, 23% of patients (n = 77) experienced serious adverse events, among which only 1 event was drug-related (0.3%). No differences in overall adverse events, serious adverse events, and deaths were observed between Child-Pugh A and Child-Pugh B patients. The most frequent drug-related adverse events were dermatological/skin (24%), hand-foot skin reaction (20%), gastrointestinal (11%), and diarrhea (11%). The majority of adverse events occurred within 30 days of beginning sorafenib.ConclusionSorafenib has satisfactory efficacy and safety in Chinese Child-Pugh A and B patients with unresectable HCC using the recommended dosage of 800 mg/day, and the safety of sorafenib is not affected by liver function. Prophylaxis for gastrointestinal adverse events may help to decrease dose interruptions or discontinuation.Trial registrationClinicalTrials.gov; Identifier: NCT00812175. Date of registration: December 19, 2008.

Observational registry of sorafenib use in clinical practice across Child-Pugh subgroups: The GIDEON study

GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib) is a prospective, observational registry study evaluating the safety of sorafenib and treatment practices in hepatocellular carcinoma patients. This large global database allowed for assessment of the use and tolerability of sorafenib in patients with liver dysfunction. Baseline characteristics and medical/treatment history were collected in patients for whom a decision to treat with sorafenib had been made. Adverse event, dosing, and outcomes data were collected during follow-up. In the overall safety population (n=3202), 1968 patients (61%) had Child-Pugh A status and 666 (21%) had Child-Pugh B. The majority of Child-Pugh A (72%) and Child-Pugh B (70%) patients received an initial sorafenib dose of 800mg, consistent with the label, and dose reduction rates were 40% and 29%, respectively. The type and incidence of adverse events were generally consistent across Child-Pugh subgroups. The incidence of drug-related adverse events leading to discontinuation was similar between Child-Pugh A and Child-Pugh B patients (17% and 21%). In the intent-to-treat population (n=3213), median overall survival (months [95% confidence interval]) was longer in Child-Pugh A patients (13.6 [12.8-14.7]) compared with Child-Pugh B patients (5.2 [4.6-6.3]). In clinical practice, the safety profile of sorafenib appeared to be consistent across Child-Pugh A and Child-Pugh B patients. Findings suggest sorafenib may be safely used in some Child-Pugh B patients and indicate the importance of careful patient evaluation when making treatment decisions. The GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib) study is a large prospective registry of patients with liver cancer who were treated with sorafenib. The aims were to evaluate the safety and tolerability of sorafenib among those in which the liver was not functioning properly. The study showed that the safety profile of sorafenib was consistent across patients with preserved liver function and those in which the liver was not functioning properly, and therefore, suggesting that sorafenib may be a valid treatment for some patients with liver impairment.

Regional differences in sorafenib-treated patients with hepatocellular carcinoma: GIDEON observational study.

Treatment approaches for hepatocellular carcinoma (HCC) vary across countries, but these differences and their potential impact on outcomes have not been comprehensively assessed. Data from the multinational GIDEON (Global Investigation of therapeutic DEcisions in HCC and Of its treatment with sorafeNib) registry evaluated differences in patient characteristics, practice patterns and outcomes in HCC across geographical regions in patients who received sorafenib. GIDEON is a non-randomised, observational registry study conducted in 39 countries across five global regions. HCC patients in whom a decision to treat with sorafenib was made in clinical practice and according to local practices were included. 3202 patients were evaluable for safety analysis: Asia-Pacific (n = 928), Japan (n = 508), Europe (n = 1113), USA (n = 563) and Latin America (n = 90). Patients in Japan had earlier-stage disease at initial diagnosis compared with patients in other regions (Barcelona Clinic Liver Cancer stage A; 43.7% vs 9.1-24.3%). Use of locoregional therapies before sorafenib, including transarterial chemoembolisation, was more common in Japan (84.4%) and Asia-Pacific (67.2%) compared with the USA (49.4%) and Europe (43.5%). Treatment patterns with respect to sorafenib also differed, with a shorter duration of treatment reported in the USA and Asia-Pacific. Time from initial diagnosis to death was longer in Japan compared with other regions (median, 79.6 months vs 14.8-25.0 months). Data from GIDEON highlight regional variations in the management of HCC and patient outcomes. Greater standardisation of management may help optimise outcomes for HCC patients.

Therapeutic decisions and treatment with sorafenib in hepatocellular carcinoma: final analysis of GIDEON study in Italy

Sorafenib, an oral multikinase inhibitor, is the only targeted agent approved for the treatment of patients with hepatocellular carcinoma (HCC) after demonstration to increase overall survival compared to placebo in two randomized phase III study. GIDEON (Global Investigation of therapeutic DEcisions in HCC and Of its treatment with sorafeNib) is the largest, global, non-interventional, prospective study of patients with uHCC (n>3200) treated with sorafenib in real-life clinical practice conditions. Here we report the final analysis of safety and efficacy in the Italian cohort of patients. Patients with unresectable HCC who are candidates for systemic therapy, and for whom a decision has been made to treat with sorafenib, are eligible for inclusion. Patients demographics disease characteristics and treatment history were recorded at baseline visit. Sorafenib dose, concomitant medications, performance status, liver function, adverse events and efficacy (survival and response rate) were collected throughout the study. In the Italian cohort of the GIDEON study 278 patients were included in 36 centers. The global rate of adverse events was 81%. Drug-related events accounted for 67%, mostly of grade 1 and 2, and only 8% were classified as serious. The most common were diarrhea (24%), fatigue (23%), dermatological (14%), rash/exfoliation (10%), hypertension (9%), hemorrage/bleeding of gastrointestinal tract (6%). Overall survival was 14.4 months and time to progression 6.2 months. Objective responses were observed in 14 patients (5%) with 3 complete responses (1%). Stable diseases of at least 6 weeks were observed in 113 patients (41%) with a 30% of disease control rate. The safety profile of sorafenib in terms of rate and type of adverse events is similar to that emerged in the global international GIDEON study as well as in the pivotal registration studies.

Real-Life Experience of Sorafenib Treatment for Hepatocellular Carcinoma in Korea: From GIDEON Data.

PurposeThe purpose of this study is to report real life experiences of sorafenib therapy for hepatocellular carcinoma (HCC) in Korea, using a subset of data from GIDEON (Global Investigation of Therapeutic Decisions in HCC and of Its Treatment with Sorafenib; a large, prospective, observational study).Materials and MethodsBetween January 2009 and April 2012, a total of 497 patients were enrolled from 11 sites in Korea. Of these, 482 patients were evaluable for safety analyses. Case report forms of paper or electronic version were used to record safety and efficacy data from all patients.ResultsMore patients of Child-Pugh A received sorafenib for > 8 weeks than did patients of Child-Pugh B (55.5% vs. 34.3%). Child-Pugh score did not appear to influence the starting dose of sorafenib, and approximately 70% of patients both in Child-Pugh A and B groups received the recommended initial daily dose of 800 mg (69.0% and 69.5%, respectively). The median overall survival (OS) and time to progression (TTP) were 8.5 months and 2.5 months. In Child-Pugh A patients, the median OS and TTP were 10.2 months and 2.5 months. The most frequent treatment-emergent drug-related adverse event was hand-foot skin reaction (31.7%), followed by diarrhea (18.0%). The incidence of treatment-emergent adverse events was similar in both Child-Pugh A (85.4%) and Child-Pugh B (84.8%) patients.ConclusionSorafenib was well tolerated by Korean HCC patients in clinical settings, and the safety profile did not appear to differ by Child-Pugh status. Survival benefit in Korean patients was in line with that of a previous pivotal phase III trial (SHARP).

Use of Transarterial Chemoembolization (TACE) and Sorafenib in Patients with Unresectable Hepatocellular Carcinoma: US Regional Analysis of the GIDEON Registry

Background: Global Investigation of Therapeutic Decisions in Hepatocellular Carcinoma and of Treatment with Sorafenib (GIDEON) is a worldwide, prospective, non-interventional study to evaluate the safety of sorafenib in a variety of patient subsets. Methods: Eligible patients had unresectable hepatocellular carcinoma for whom the decision had been made to treat with sorafenib. Treatment strategies were instituted at the physician's discretion. Patient and disease characteristics, treatment practices, incidences of adverse events (AEs), and overall survival were collected. Results: In the United States, 563 patients were evaluable for safety. Subgroup analysis was performed for patients who underwent transarterial chemoembolization (TACE) prior to the initiation of sorafenib (group A, n=158), after the initiation of sorafenib only (group B, n=29), both (group C, n=38), or did not undergo TACE (n=318). Patient demographics were similar across the groups. In group A, 29% had Child-Pugh score B or C at diagnosis, and 19% had Barcelona Clinic Liver Cancer tumor stage C or D. In group B, 48% had Child-Pugh score B or C at study entry, and 31% had BCLC stage C or D. The majority of patients in all groups initially received full-dose sorafenib. Incidences of grade ≥3 drug-related AEs were 30%, 17%, and 16% in groups A, B, and C, respectively, and 22% in patients who did not undergo TACE. No new safety signals emerged. Conclusions: The results from GIDEON reaffirm that sorafenib can be safely used in the context of TACE.

P-111 Final results of the GIDEON (Global Investigational of therapeutic DEcisions in HCC and Of its treatment with sorafeNib) study according to patient etiology: The Italian experience

Introduction: Sorafenib is the only targeted agent indicated for the treatment of hepatocellular carcinoma (HCC). The global, prospective, non-interventional GIDEON study enrolled over 3200 patients (pts) with unresectable HCC (uHCC) treated with sorafenib in real-life clinical practice conditions. The primary objective of the study was to evaluate the safety of sorafenib in HCC patients in clinical practice. Secondary objective was efficacy. We report the final analysis of the Italian subgroup of patients according to etiology. Methods: Patients with uHCC for whom the decision to administer sorafenib was taken were eligible for enrollment. Disease and patient characteristics were assessed at baseline. Sorafenib dose, adverse events (AEs) and disease assessments were reported at follow-up. Results: Of 278 pts enrolled in Italy, 274 were evaluable for efficacy and 271 for safety analysis. The median age was 70 years (range: 44-90), 227 pts (83%) were male, 266 pts (97%) Caucasian and disease stage was BCLC-B in 87(32%) and BCLC-C in 142(52%) pts. The etiology of the underlying liver disease was recorded as hepatitis B (hep-B) in 58(21%) pts, hep B only in 39(14%) pts, hepatitis C (hep-C) in 157(57%), hep-C only in 119(43%) pts, alcohol use in 112(41%) pts and nonalcoholic steatohepatitis (NASH) in 7(2.6%) pts. Overall adverse events were slightly more frequent in pts with hep-B (88%) than those with hep-C (75%) or alcohol use (75%). The type and incidence of AEs were consistent among all subgroups, the most frequent being gastrointestinal (diarrhea/ascites), dermatologic (hand-foot skin reaction/rash) and fatigue. There were no new unexpected AEs. Median OS in days (months) in pts with hep-B, hep-C, alcohol use, NASH, hep-B only and hep-C only were 351(11.5), 617(20.5), 402(13.1), 211(6.9), 351(11.5) and 633(20.7) respectively. Conclusion: The most frequent etiology was hep-C followed by alcohol use and hep-B. Safety was consistent with the known profile of sorafenib. Overall survival was longer in the subgroup of hep-C pts than in the other etiology subgroups. This has also been reported in previous analyses. Table: P-111

Localized and systemic approaches to treating hepatocellular carcinoma.

Although hepatocellular carcinoma (HCC) is the sixth most common cancer globally, the overall outcomes are poor with 5-year overall survival (OS) rates estimated at less than 12%. Relatively few patients are eligible for curative therapy because of the late appearance of symptoms despite the established efficacy of screening programs in at-risk individuals. Unlike other high-incidence malignancies, therapeutic decisions in HCC are hampered by the limits of high-quality evidence across all clinical scenarios. The selection of treatment modalities depends not only on the stage, the extent of tumor, and the patient’s performance status but also on the underlying liver function. The Barcelona Clinic Liver Cancer (BCLC) classification stratifies patients according to these factors and provides treatment recommendations (Fig 1), but it may oversimplify decision making that is best approached through multidisciplinary case discussions. Surgery or transplantation remain the mainstays of curative therapy for early disease. Ablative strategies can also cure small tumors. Transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and external beam radiation therapy (EBRT) can control locally advanced disease no longer amenable to cure. Systemic treatment for advanced HCC was not recognized as a standard until the approval of sorafenib for a modest improvement in median OS. This discovery resulted in a plethora of clinical trials aimed at advancing the field. Many targeted therapies are being explored as firstor second-line treatment options in advanced HCC, although results to date have been disappointing. Because more than 90% of cancers arise in patients with underlying cirrhosis, the treatment of HCC requires the management of both the concurrent malignancy and liver disease. Many patients presenting with HCC will require ongoing supportive care of their underlying liver disease such as hepatitis B virus (HBV) or hepatitis C virus (HCV) infections or nonalcoholic steatohepatitis. Because these conditions may also complicate cancer treatment strategies (eg, with a high risk for reactivation of HBV around most cancer treatments), antiviral therapy for active infection should be considered a standard of care. Because HCV does not generally reactivate around cancer treatments, dedicated therapy is not necessary. However, the current advancements in new direct-acting antivirals such as sofosbuvir and others are so effective that shorter courses of therapy are associated with high sustained HCV response rates with relatively few toxicities. It is expected that patients with HCV will be treated early for viral clearance precirrhosis, even if they present later with HCC.

Sorafenib use in hepatocellular carcinoma: More questions than answers

Sorafenib use in hepatocellular carcinoma: More questions than answers

Final analysis of European patients from the Global Investigation of Therapeutic Decisions in Hepatocellular Carcinoma and of its Treatment with Sorafenib (GIDEON) study: Baseline characteristics and staging systems.

4088 Background: The global, prospective, non-interventional GIDEON study recruiting >3,000 patients with unresectable hepatocellular carcinoma treated with sorafenib is complete. We report the fin...

GIDEON (Global Investigation of therapeutic DE cisions in hepatocellular carcinoma and Of its treatment with sorafeNib): second interim analysis

BackgroundGIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma [HCC] and Of its treatment with sorafeNib) is a global, prospective, non-interventional study undertaken to evaluate the safety of sorafenib in patients with unresectable HCC in real-life practice, including Child-Pugh B patients who were excluded from clinical trials.MethodsPatients with unresectable HCC, for whom the decision to treat with sorafenib, based on the approved label and prescribing guidelines, had been taken by their physician, were eligible for inclusion. Demographic data and disease/medical history were recorded at entry. Sorafenib dosing and adverse events (AEs) were collected at follow-up visits. The second interim analysis was undertaken when ∼1500 treated patients were followed up for ≥ 4 months.ResultsOf the 1571 patients evaluable for safety, 61% had Child-Pugh A status and 23% Child-Pugh B. The majority of patients (74%) received the approved 800 mg initial sorafenib dose, regardless of Child-Pugh status; however, median duration of therapy was shorter in Child-Pugh B patients. The majority of drug-related AEs were grade 1 or 2, and the most commonly reported were consistent with previous reports. The incidence and nature of drug-related AEs were broadly similar across Child-Pugh, Barcelona Clinic Liver Cancer (BCLC) and initial dosing subgroups, and consistent with the overall population.ConclusionsConsistent with the first interim analysis, overall safety profile and dosing strategy are similar across Child-Pugh subgroups. Safety findings also appear comparable irrespective of initial sorafenib dose or BCLC stage. Final analyses in > 3000 patients are ongoing.

Final analysis of GIDEON (Global Investigation of Therapeutic Decisions in Hepatocellular Carcinoma [HCC] and of Its Treatment with Sorafenib [Sor]) in >3000 Sor-treated patients (pts): Clinical findings in pts with liver dysfunction.

4126 Background: GIDEON is a prospective, non-interventional study. Completion of GIDEON creates a large, global database of >3000 Sor-treated unresectable HCC (uHCC) pts, allowing for evaluation of a broad pt population, including Child-Pugh (CP) B pts with more advanced liver dysfunction. Methods: Baseline characteristics were collected in pts for whom a decision to treat with Sor had been made in clinical practice. Adverse events (AEs), dosing, and outcomes data were collected during follow-up. Results: 3,202 pts were evaluable for safety. Overall, the incidence of AEs and drug-related (DR) AEs was similar across CP subgroups, although serious AEs (SAEs) were more common in CP-B than CP-A pts. The rate of DR AEs (event per patient-year) was also comparable between CP-A and CP-B pts. The average daily Sor dose was slightly higher in CP-B than CP-A pts; duration of treatment was longer in CP-A (Table). In the intent-to-treat population (n=3,213), median overall survival (OS) (months [95% CI]) was longer in CP-A (13.6 [12.8-14.7]) than CP-B pts (5.2 [4.6-6.3]); time to progression was similar: CP-A (4.7 [4.3-5.2]); CP-B (4.4 [3.5-5.5]). Median OS was shorter in pts with a higher CP-B score: 7 (6.2 [4.9-8.7]); 8 (4.8 [4.1-6.9]); 9 (3.7 [3.0-5.1]). Conclusions: Sor safety and dosing during treatment are generally consistent across pts irrespective of liver function. As anticipated, CP status is a strong prognostic factor for OS in uHCC pts. [Table: see text]

Erratum

International Journal of Clinical PracticeVolume 66, Issue 9 p. 912-912 ERRATUMFree Access Erratum This article corrects the following: First interim analysis of the GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib) non-interventional study R. Lencioni, M. Kudo, S.-L. Ye, J.-P. Bronowicki, X.-P. Chen, L. Dagher, J. Furuse, J. F. Geschwind, L. L. de Guevara, C. Papandreou, A. J. Sanyal, T. Takayama, S. K. Yoon, K. Nakajima, F. Cihon, S. Heldner, J. A. Marrero, Volume 66Issue 7International Journal of Clinical Practice pages: 675-683 First Published online: June 15, 2012 First published: 17 August 2012 https://doi.org/10.1111/ijcp.12005AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Original paper “First interim analysis of the GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib) non-interventional study”. Int J Clin Pract 2012; 66: 675–683. A co-author’s name was incorrectly printed as L.L de Guevara. The correct name is L. Ladrón de Guevara. Also, in the results section, under sorafenib administration by Child-Pugh status, the sentence “Duration of treatment was generally shorter in Child-Pugh A than in Child-Pugh B patients.” should read “Duration of treatment was generally shorter in Child-Pugh B than in Child-Pugh A patients.” All other data in the paragraph, in the relevant table and the remainder of the paragraph are correct. Reference 1 Lencioni R, Kudo M, Ye S-L, Bronowicki J-P, Chen X-P, Dagher L, Furuse J, Geschwind JF, Ladrón de Guevara L, Papandreou C, Sanyal AJ, Takayama T, Yoon SK, Nakajima K, Cihon F, Heldner S, Marrero JA. First interim analysis of the GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib) non-interventional study. Int J Clin Pract 2012; 66: 675– 683. Volume66, Issue9September 2012Pages 912-912 ReferencesRelatedInformation

777TiP - Second Interim Analysis of the Global Investigation of Therapeutic Decisions in Hepatocellular Carcinoma and of its Treatment with Sorafenib (GIDEON) Study According to Disease Stage

ABSTRACT Background GIDEON (NCT00812175) is an ongoing, global, prospective, non-interventional study of patients with unresectable hepatocellular carcinoma (HCC) receiving sorafenib (Nexavar®) in real-life practice. The aim is to evaluate sorafenib safety and efficacy in diverse settings and patient groups. The second interim analysis was triggered when ∼1500 patients had been treated for ≥ 4 months. We describe sorafenib use in Europe according to disease stage. Methods Patient/disease characteristics (including Barcelona Clinic Liver Cancer [BCLC], tumour node metastases [TNM], Cancer for the Liver Italian Programme [CLIP]) and treatment history were recorded at enrolment; sorafenib dose, concomitant medications, performance status, liver function, adverse events (AEs) and efficacy are recorded at follow-up visits. Results Of 1571 patients in the safety population, 588 are in Europe (see table). The majority of patients were BCLC-C (52.9%), TNM III (40.3%) or CLIP 1/2 (26.0%/25.9%), although sorafenib was also used in patients with early, intermediate and end-stage disease. Generally, AEs and serious AEs (SAEs) increased with advancing disease (AEs: 66.0%, 87.4%, 85.5%, 89.7%; SAEs: 22.6%, 37.8%, 38.3%, 58.6%; for BCLC-A, B, C and D; respectively), whereas sorafenib-related AEs and SAEs were comparable across BCLC groups (AEs: 60.4%, 74.1%, 68.5%, 41.4%; SAEs: 7.5%, 15.4%, 10.3%, 10.3%; for BCLC-A, B, C and D; respectively). Evaluation will continue with more mature data. Medical oncologist (n = 189) Hepatologist/ GI specialist (n = 332) EU total (n = 588) BCLC stage at study entry, % of n A 6.9 8.7 9.0 B 19.6 27.7 24.3 C 59.3 50.6 52.9 D 3.2 5.4 4.9 NE/missing 11.1 7.5 8.8 TNM stage at study entry, % of n I 3.2 10.5 8.8 II 8.5 12.3 10.2 III 39.2 41.9 40.3 IV 40.2 19.9 26.9 NE/missing 9.0 15.4 13.8 Child-Pugh score at start of sorafenib therapy, % of n A 68.3 64.8 66.3 B 13.8 26.8 21.6 C 1.1 1.8 1.5 NE/missing 16.9 6.6 10.5 CLIP score at start of sorafenib therapy, % of n 0 14.8 8.4 11.9 1 24.3 26.5 26.0 2 24.3 26.5 25.9 3 5.8 15.7 11.4 4–6 4.2 11.4 8.7 NE/missing 26.5 11.4 16.2 NE, not evaluable Conclusions These data reflect real-world sorafenib given to a broad range of patients, indicating a similar safety profile across the different disease stages. Evaluation is ongoing, with more mature data expected from the final analysis. Disclosure B. Daniele: Dr B. Daniele has participated in advisory boards and received lecture fees from Bayer. J. Turnes: Dr J Turnes has participated in advisory boards for Roche Pharma. C. Papandreou: Prof. C Papandreou has participated in advisory boards for Bayer, Sanofi Aventis, Novartis, Bristol Meyers Squibb and Janssen. P. Stal: Prof. Stal has advised and received a grant from Bayer. A. Croitoru: Dr A Croitoru has consulted for and received an investigator fee from Bayer. P: Mathurin: Dr. P . Mathurin was paid speaking at symposia for Roche, Schering-Plough, Gilead Sciences, Bristol-Myers Squibb, Janssen-Cilag and Bayer Healthcare pharmaceutical companies. He is an investigator for Roche, Schering-Plough, Bristol-Myers Squibb, Gilead Sciences, Vertex pharmaceuticals Janssen-Cilag, Boeringher, Novartis and Bayer Healthcare companies. He is a member of the French boards of experts in Hepatology for Roche Schering-Plough, Gilead Sciences, Bayer Healthcare and Bristol-Myers Squibb pharmaceutical companies. He is consulting for the Gilead Sciences, Bristol-Myers Squibb, Bayer Healthcare and Vertex pharmaceutical Companies. All other authors have declared no conflicts of interest.

670PD - Gideon (Global Investigation of Therapeutic Decisions in Hepatocellular Carcinoma [HCC] and of Its Treatment with Sorafenib [SOR]) 2nd Interim Analysis (IA): Subgroup Analysis by Disease Etiology

ABSTRACT Background GIDEON is an ongoing, global, prospective non-interventional study of unresectable HCC pts receiving Sor in real-life practice. We present results of a descriptive, subgroup analysis by leading disease etiology. Methods Demographics/medical/disease history are recorded at study entry; adverse events (AEs) and efficacy at follow-up. Over 3000 pts were enrolled from 39 countries. Per protocol the 2nd IA was planned when ∼1500 treated pts were followed ≥4 months. Results In the safety population (N = 1571, 588 from Europe), leading disease etiologies were alcohol use (47%), hepatitis B virus (HBV; 37%), and hepatitis C virus (HCV; 32%). There were regional differences in liver disease etiology. Alcohol use was more common in the US (41%) and Europe (36%) than in Asia-Pacific (AP; 20%). HBV was more common in AP (83%); HCV was more common in the US (53%) and Japan (55%). Across etiologic subgroups, most pts were male (76-93%) and had Eastern Cooperative Oncology Group performance status 0 or 1 (83-84%). At study entry, more HBV pts (68%) had advanced Barcelona Clinic Liver Cancer stage (C or D) than HCV pts (51%). Safety data were comparable across etiologies. Preliminary median survival from initial diagnosis or first Sor dose (intent-to-treat population, N = 1612) was shorter for HBV and alcohol use pts than for HCV pts: time from initial diagnosis to death, 35.2 [95% CI 27.6-50.0], 25.6 [95% CI 19.0-36.8], and 45.6 [95% CI 33.0-64.8] months, respectively; overall survival (OS) from first Sor dose, 7.9 [95% CI 6.6-9.3], 8.1 [95% CI 6.9-8.7], and 9.5 [95% CI 8.4-12.6] months, respectively. Treatment-emergent AEs, %a Total (N = 1571) Alcohol use (n = 746) HBV (n = 575) HCV (n = 504) AEs 83 86 78 88 Drug-related AEs 64 64 57 71 Serious AEs 37 41 32 40 Drug-related serious AEs 9 9 5 12 Deaths 22 25 19 20 aMissing data not shown. Conclusions Preliminary 2nd IA results indicate HBV pts have more advanced disease at study entry than HCV pts. The lower median OS in HBV pts may reflect their poorer prognosis and natural history. Sor safety profile does not appear to be influenced by liver disease etiology. Disclosure J. Bronowicki: Bayer consultation and speaker fees. J. Marrero: Consultant for Bayer HealthCare Pharmaceuticals and Onyx; advisory committee/review panel member for Bayer HealthCare Pharmaceuticals and Onyx; Research grant received from Bayer HealthCare Pharmaceuticals. K. Nakajima: Employee of Bayer HealthCare, Own stocks. R. Lencioni: Lecture fees, Bayer Healthcare. All other authors have declared no conflicts of interest.

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

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. 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. 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. 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.

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

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.

Abstract No. 196: Worldwide trends in locoregional therapy (LRT) for hepatocellular carcinoma (HCC): 2nd interim analysis (IA; 1500 patients [pts]) of the GIDEON (global investigation of therapeutic decisions in HCC and of its treatment with sorafenib) study

Abstract No. 196: Worldwide trends in locoregional therapy (LRT) for hepatocellular carcinoma (HCC): 2nd interim analysis (IA; 1500 patients [pts]) of the GIDEON (global investigation of therapeutic decisions in HCC and of its treatment with sorafenib) study

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: &gt;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]

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)