1. Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib (GIDEON) study

2. Introduction
Sorafenib is the only systemic therapy indicated to treat HCC1-4
In two Phase III studies (SHARP and Asia-Pacific), sorafenib significantly improved OS in patients with uHCC5-6
GIDEON allows evaluation of several clinically relevant patient subgroups, including those with more advanced liver dysfunction in whom data were previously limited
GIDEON was the largest prospective study in uHCC ever conducted7
Over 3000 patients have been enrolled from 39 countries8
uHCC, unresectable hepatocellular carcinoma; OS, overall survival;
1.NCCN Guidelines™: Hepatobiliary Cancers. Available at: Accessed May 29, EASL–EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma Journal of Hepatology 2012 vol. 56 j 908–943 Available on: Position paper AISF DLD (2013) AIOM Guidelines. Available at: 5. Llovet JM, et al. N Engl J Med. 2008;359(4): Cheng AL, et al. Lancet Oncol. 2009;10(1): Lencioni R, et al. Int J Clin Prac. 2010;64(8):
8. Marrero JA et al. Abstract presented at AASLD 2011 Annual Meeting

3. The GIDEON study: design and objectives
The GIDEON study is a large, global, prospective, non- interventional study of patients with unresectable HCC who are eligible for systemic therapy and for whom the decision has been taken to treat with sorafenib under real-life practice conditions.
Primary objective: The primary objective of GIDEON is to evaluate the safety of sorafenib in uHCC patients under real-life clinical practice conditions and to gather more comprehensive data on the use of sorafenib in patients with Child-Pugh B liver function, who were excluded from the randomised clinical trials.
Secondary objectives: evaluate the efficacy [OS, progression-free survival (PFS), time to progression (TTP), response rate and stable disease rate] of sorafenib; determine the duration of therapy according to various patient characteristics; evaluate methods of patient evaluation, diagnosis and follow-up; assess comorbidities and their influence on treatment and outcome in real-life practice rather than a controlled clinical trial setting and evaluate the practice patterns of the physicians involved in the care of these patients.
Lencioni R, et al. Int J Clin Prac. 2010;64(8):

4. The GIDEON study: design and objectives
Planned subgroup analyses conducted globally, regionally and by country will include:
the impact of baseline characteristics on safety, particularly Child-Pugh B;
the relationship between baseline characteristics and efficacy;
the duration of sorafenib therapy and reasons for discontinuation;
the effect of other treatments for HCC on outcome and the impact of different practice patterns on outcome.
Lencioni R, et al. Int J Clin Prac. 2010;64(8):

5. The GIDEON study: Patient eligibility
Eligibility criteria include:
Patients with histologically or cytologically documented or radiographically diagnosed unresectable HCC who are candidates for systemic therapy, and for whom a decision has been made to treat with sorafenib
life expectancy of > 8 weeks
Have provided signed informed consent.
Lencioni R et al. Int J Clin Pract 2010;64:1034–4

6. The GIDEON study: safety, efficacy, treatment and baseline patient assessments and end-points
Adverse events
Relation
Seriousness
NCI-CTC grade
Action taken
Outcome
Child-Pugh score
ECOG PS
Efficacy OS
TTS
PFS RR SD
Treatment for HCC
Sorafenib therapy
Duration of treatment
Reason for discontinuation
Other therapies
Prior
Concurrent
Following Sorafenib
Baseline characteristics
History of HCC
Duration from initial diagnosis
Disease extent
Stage (BCLC, TNM, CLIP)
Tumor burden, presence of metastasis
Previous treatment
Aetiology
Liver disorders
Child-Pugh, cirrhosis
Age, gender, race
Co-morbidities
BCLC, Barcellona Clinic Liver Cancer; CLIP, Cancer of the Liver Italian Program; ECOG, Eastern Cooperative Oncology Group performance status; HCC, hepatocellular carcinoma; NCI-CTC, National Cancer Institute-Common Toxicity Criteria; OS, overall survival; PFS, progressio-free survival; RR, rensponse rate; SD, stable disease; TNM, tumor node metastases; TTP, time to progression
Lencioni R et al. Int J Clin Pract 2010;64:1034–41

7. The GIDEON study: timeline and planned analyses
2010
Phase I
Objectives:
Phase II
Phase III
Phase IV and V
Site initiation
Study initiation
Safety assessment in Child-Pugh B
First interim analysis (500 patients)
Second interim analysis (1500 patients)
Efficacy assessment of sorafenib in a board population of patients with HCC
3000th patient
Last patient’s last visit 31 December 2013
Analysis of final data
- Safety
- Efficacy
Provide data to regolatory organizations
Lencioni R et al. Int J Clin Pract 2010;64:1034–41

8. GIDEON study: regional distribution of patients
A total of 3371 patients were enrolled from 39 countries, across 5 different regions
Marrero J, et al. J Clin Oncol 31, 2013 (suppl; abstr 4126)

9. GIDEON final analysis patients population
3202 patients in the safety population
Safety population used for analysis of AEs and serious AEs
3213 patients in the ITT population
ITT population used for analysis of OS and TTP
ITT, intent to treat; OS, overall survival; TTP, time-to-progression
Marrero J, et al. J Clin Oncol 31, 2013 (suppl; abstr 4126)

10. GIDEON final analysis: baseline patients characteristics by CP status
% of n
Child-Pugh A (n=1968)
Child-Pugh B (n=666)
Child-Pugh C (n=74)
total (n=3202)*
Number of patients
615
208 23
100
Male/female
82/18
81/19
Median age, years 64 61 58 62
ECOG PS
0 or 1 88 72 59 83
>2 7 21 34 12
TNM stage I 5 4 II 15 9 14
III 36 43 35 IV 33 30
BCLC stage A 8 6 B 22 20 C 57 56 1 52 D 3 89
*includes 493 non-evaluable patients
BCLC, Barcelona Clinic Liver Cancer; ECOG PS, Eastern Cooperative Oncology Group performance status; TNM, tumor node metastasis
Marrero J, et al. J Clin Oncol 31, 2013 (suppl; abstr 4126)

11. GIDEON final analysis: overall treatment-emergent safety data by CP status
% of n
Child-Pugh A (n=1968)
Child-Pugh B (n=666)
Child-Pugh C (n=74)
total (n=3202)a
AEs (all grades) 84
88.6
91.9
85.3
Drug-related AEs (all grades)
68.5
64.4
39.2
66.0
Serious AEsb (all grades)
36.0
60.4
70.3
43.3
Drug-related serious AEs (all grades)
8.8
14.1
2.7
9.3
All grade 3 or 4
32.5
31.6
17.6
31.8
Drug-related grade 3 or 4
25.5
22.0
10.8
23.6
AEs resulting in permanent discontinuation of sorafenib
28.9
40.1
43.2
31.4
Deathsc
17.7
35.9
51.4
23.7
Patients who received >1 dose of sorafenib and had >1 follow-up assessment were included in the safety analysis.
aIncludes 493 non-evaluable patients; bAny AE occurring at any dose that results in any of the following outcomes: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; medically important event; cTreatment-emergent deaths occurring up to 30 days after last sorafenib dose
Marrero J, et al. J Clin Oncol 31, 2013 (suppl; abstr 4126)

12. GIDEON final analysis: rate of drug-related AEsa by CP status
Rate, event per patient-yeara
Child-Pugh A (n=1968)
Child-Pugh B (n=666)
Child-Pugh C (n=74)
Total
(n=3202)b
Any AE
1.17
25.5
1.41
1.24
Diarrhea
0.48
0.39
0.51
HFSR
0.54
17.0
0.19
0.50
Fatigue
0.27
14.3
0.49
0.29
Rash / desquamation
0.21
8.6
0.15
Anorexia
0.18
7.4
0.24
Nausea
0.09
6.2
0.34
0.12
Pain, abdomen, NOS
0.05
3.6
0.06
Liver dysfunction
0.03
aRate calculation based on treatment-emergent AEs with >10% incidence and days per year; bIncludes 493 non-evaluable patients
Marrero J, et al. J Clin Oncol 31, 2013 (suppl; abstr 4126)

13. GIDEON final analysis: onset time of AEs > grade 3 by CP status
Time to AE onset (days)
Child-Pugh A
Child-Pugh B
The onset time of AEs was comparable between Child-Pugh A and Child-Pugh B patients, with the majority of AEs occurring within the first 30 days of treatment in both groups
Marrero J, et al. J Clin Oncol 31, 2013 (suppl; abstr 4126)

14. GIDEON final analysis: sorafenib dosing and treatment duration by CP status
Child-Pugh A (n=1968)
Child-Pugh B (n=666)
Child-Pugh C (n=74)
total (n=3202)a
Initial dose of 800 mg, % of 84
88.6
91.9
85.3
Initial dose of 400 mg, % of n
68.5
64.4
39.2
66.0
Median daily dose, mg
36.0
60.4
70.3
43.3
Median treatment duration, weeks
8.8
14.1
2.7
9.3
Overall and across Child-Pugh subgroups, the majority of patients received the recommended initial dose of 800 mg
The median daily dose was similar across Child-Pugh subgroups
Duration of treatment was longer in Child-Pugh A patients than in Child-Pugh B patients
aIncludes 493 non-evaluable patients
Marrero J, et al. J Clin Oncol 31, 2013 (suppl; abstr 4126)

15. GIDEON final analysis: duration of sorafenib treatment by CP status
Child-Pugh A
Child-Pugh B
Overall, the majority of patients received sorafenib for either ,8 weeks (29.5%) or >24 weeks (35.9%), and 31.2% of patients received sorafenib for >28 weeks
In Child-Pugh B patients treated with sorafenib, 25.7% were treated for 24 weeks
Marrero J, et al. J Clin Oncol 31, 2013 (suppl; abstr 4126)

16. GIDEON final analysis: OS by CP status
Overall survival
Median overall survival (OS; months) was longer in Child-Pugh A patients than in Child-Pugh B and C patients (13.6 vs 5.2 and 2.6, respectively)
CI, confidence interval
Marrero J, et al. J Clin Oncol 31, 2013 (suppl; abstr 4126)

17. GIDEON final analysis: TTP by CP status
Time to progression
Time to progression (TTP) was comparable between Child-Pugh A and B patients
The imaging examination interval was at the investigators’ discretion
Marrero J, et al. J Clin Oncol 31, 2013 (suppl; abstr 4126)

18. GIDEON final analysis: OS by BCLC stage
Overall survival
Patients with BCLC stage A had a median OS ~3 times that of patients with BCLC stage C
Bronovicki J-P, et al. Presented at ECC P 2594

19. GIDEON final analysis: TTP by BCLC stage
Time to progression
Bronovicki J-P, et al. Presented at ECC P 2594

20. GIDEON final analysis: OS by TNM stage
Overall survival
Median OS (months) was similar across TNM stages IIIA, IIIB, IIIC, and IV (9.5 vs 9.2 vs 10.8 vs 9.1)
TNM, tumor node metastasis
Bronovicki J-P, et al. Presented at ECC P 2594

21. GIDEON final analysis: TTP by TNM stage
Time to progression
TNM, tumor node metastasis
Bronovicki J-P, et al. Presented at ECC P 2594

22. GIDEON final analysis: OS by ECOG performance status
Overall survival
Median OS was greater in patients with an ECOG PS of 0 or 1 than in patients with an ECOG PS of 2 or 3
Bronovicki J-P, et al. Presented at ECC P 2594

23. GIDEON final analysis: TTP by ECOG performance status
Time to progression
Bronovicki J-P, et al. Presented at ECC P 2594

24. Conclusions
The safety profile of sorafenib in uHCC patients appears consistent, irrespective of liver function
AEs observed across Child-Pugh subgroups were in keeping with the known AE profile of sorafenib
Child-Pugh status does not appear to influence the approach to sorafenib dosing, although duration of treatment is shorter in Child-Pugh B patients than in Child-Pugh A patients
Discontinuation of sorafenib due to AEs is higher in Child-Pugh B patients
Consistent with previous reports, Child-Pugh status is a strong prognostic factor for OS in uHCC patients, regardless of treatment with sorafenib
TTP was similar in Child-Pugh A and Child-Pugh B patients, while OS was longer in Child-Pugh A patients
Marrero J, et al. J Clin Oncol 31, 2013 (suppl; abstr 4126)

25. GIDEON final analysis:
the European subset
A total of 1113 patients in 22 European countries were evaluable for safety
At study initiation the majority of European patients (82.4%) started sorafenib therapy at the full prescribing dose of 800 mg/day; 15.4% received 400 mg/day of sorafenib and 2.2% received an alternative dose
*Alternative doses included 200 and 600 mg/day
Daniele B, et al. Presented at ECC P 2581

26. GIDEON final analysis - the European subset:
baseline patients characteristics by initial dose
% of n
400 mg/day (n=171)
800 mg/day (n=917)
Overall
(n=1113)
Male
84.8
83.6
83.3
Median age, years (range)
69.0 (15–90)
66.0 (19–94)
66.0 (15–94)
Etiology of underlying
liver disease, %a
Hepatitis B
18.7
18.2
18.1
Hepatitis C
36.3
34.8
35.6
Alcohol use
30.4
35.1
34.3
NASH
2.9
3.4
3.2
Unknown
17.0
17.6
17.2
ECOG PS, %
31.6
47.4
45.4 1
45.0
38.4
39.2 2
12.9
9.6
10.1 3
5.3
1.1
1.7 4
0.1
<0.1
3.6
aBaseline data collected at study entry, patients may have multiple responses;
Daniele B, et al. Presented at ECC P 2581

27. GIDEON final analysis - the European subset:
baseline patients characteristics by initial dose
% of n
400 mg/day (n=171)
800 mg/day (n=917)
Overall
(n=1113)
Child-Pugh status, %b A
58.5
66.0
64.8 B
25.7
18.8
19.9 C
1.8
1.0
1.1
Not evaluablec
14.0
14.3
BCLC stage, %b
10.5
7.5
8.5
23.4
24.3
40.9
55.9
52.9
Not evaluable/unknownd
18.7
8.3
10.0
Missinge
0.6
0.2
0.3
bAt study entry; cNecessary data for scoring were not collected in investigators’ routine practice; dNo record is available, eg transfer from other hospitals, data to assess BCLC are not available; eNo data entry on case report form for missing patients
Daniele B, et al. Presented at ECC P 2581

28. GIDEON final analysis - the European subset:
baseline patients characteristics by initial dose
% of n
400 mg/day (n=171)
800 mg/day (n=917)
Overall
(n=1113)
TNM stage, %b I
6.4
4.7
5.6 II
13.5
10.8
11.1
IIIa
34.5
30.4
31.1
IIIb
1.8
2.4
2.3
IIIc
8.2
11.6
10.9 IV
20.5
28.7
27.2
Not evaluablec
14.6
11.3
11.7
Time from initial diagnosis
to start of sorafenib therapy
Number of patients with available data
140 (81.8%)
782 (85.3%)
941 (84.6%)
Median, months
2.84
3.83
3.72
bAt study entry; cNecessary data for scoring were not collected in investigators’ routine practice
Daniele B, et al. Presented at ECC P 2581

29. GIDEON final analysis - the European subset:
history of of prior treatment by prior TACE and ctTACE
% of n
Prior TACE
n=368
No prior TACE
n=745
Concomitant TACE
n=52*
No concomitant TACE
n=1061
Overall
n=1113
Surgery
15.5
15.4
7.7
15.8
Locoregional therapy
100
15.6
78.8
41.8
43.5
TACE
73.1
34.1
33.1
RFA
26.4
9.3
17.3
14.8
14.9
HAI
1.6
0.7
1.0
PEI
8.2
3.9
3.8
5.4
5.3
Other LRTs
1.4
1.1
1.9
1.2
Systemic therapy a
3.5
Other non-systemic therapy b
*Patients in the concomitant TACE groups may also be part of the prior TACE group
aChemotherapy, immunotherapy, or others; bRadiotherapy and other locoregional therapy ct, concomitant; HAI, hepatic arterial infusion; LRT, locoregional therapy; PEI, percutaneous ethanol injection; RFA, radiofrequency ablation
P. I. Stal, et al. Presented at UEGW. P 1196

30. GIDEON final analysis - the European subset: duration of sorafenib treatment by initial dose
The duration of treatment was greater for the 800 mg/day patient group compared with the 400 mg/day patient group (18.0 vs 13.0 weeks)
*Time in weeks from initial visit to last visit date (for ongoing patients) or last dosing date +1
Daniele B, et al. Presented at ECC P 2581

31. GIDEON final analysis - the European subset: OS by initial dose
Overall survival
Patients who received an initial dose of sorafenib of 800 mg/day had greater median OS (12.1 months; 95% CI 10.5–13.8) than those patients who started on 400 mg/day (9.4 months; 95% CI 6.3–12.6)
Daniele B, et al. Presented at ECC P 2581

32. GIDEON final analysis - the European subset: OS by TACE and ct-TACE treatment
Overall survival
Median OS was greater in patients with prior TACE (464 days, 15.3 months) compared with those who did not receive prior TACE (309 days, 10.2 months)
The same result was seen in patients who received ctTACE (494 days, 16.3 months) compared with no ctTACE (336 days, 11.1 months)
P. I. Stal, et al. Presented at UEGW. P 1196

33. GIDEON final analysis: OS by underlying liver disease aetiology
Overall survival according to hepatitis B as aetiology
Overall survival according to hepatitis C as aetiology
11.7 months (358 days)
14.2 months (432 days)
Overall survival according to alcohol use
While a small advantage in OS was reported for patients with hepatitis C, TTP was comparable for each of the underlying aetiologies
12.9 months (394 days)
Ratziu V, et al. Presented at EASL P957

34. GIDEON final analysis: TTP by underlying liver disease aetiology
HCC aetiology
Median TTP, months (days)
Hepatitis B
6.5 (197)
Hepatitis C
6.0 (184)
Alcohol use
6.1 (187)
Median time to progression (TTP) in the intent-to-treat (ITT) population (n=1113) was comparable for patients with known underlying aetiologies
Ratziu V, et al. Presented at EASL P957

35. GIDEON final analysis - the European subset: rate of treatment-emergent AEs and SAEs by initial dose%
400 mg/day (n=171)
800 mg/day (n=917)
Overall*
(n=1113)
AEs (all grades)
95.9
87.8
88.3
Drug-related AEs (all grades)
73.7
68.8
Serious Aes a (all grades)
57.3
44.5
46.2
Drug-related serious AEs (all grades)
11.1
10.9
AEs resulting in permanent discontinuation of study drug
43.9
33.7
35.1
There was an increase in AEs (all grades) in the group receiving an initial dose of 400 mg/day vs 800 mg/day (95.9% vs 87.8%), and an increase in drug-related AEs (73.7% vs 68.8%) and serious Aes (57.3% vs 44.5%)
All other AE categories were comparable between the two groups
*Includes 25 patients who received an alternative dose of sorafenib; aAny AE occurring at any dose that results in any of the following outcomes: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability / incapacity; congenital anomaly / birth defect; medically important event
Daniele B, et al. Presented at ECC P 2581

36. GIDEON final analysis - the European subset: rate of treatment-emergent AEs and SAEs by prior TACE and ctTACE %
Prior TACE
n=368
No prior TACE
n=745
Ct-TACE
n=52*
No ct-TACE
n=1061
Overall
n=1113
AEs (all grades)
89.4
87.8
94.2
88.0
88.3
Drug-related AEs (all grades)
76.4
65.1
86.5
68.0
68.8
Serious AEs (all grades)
40.8
48.9
36.5
46.7
46.2
Drug-related serious AEs (all grades)
11.7
10.5
7.7
11.0
10.9
AEs resulting in permanent discontinuation of study drug
39.4
33.0
30.8
35.3
35.1
Overall, AEs and serious AEs (SAEs) were similar in the prior TACE and no prior TACE populations. The same observation was seen in the ctTACE and no ctTACE populations
The incidence of drug-related AEs was greater in patients who received prior TACE (76.4%) than those who received no prior TACE (65.1%)
The same pattern was seen for patients who had received prior ctTACE (86.5%) compared with patients who had received no ctTACE (68.0%)
*Patients in the concomitant TACE groups may also be part of the prior TACE group; aAny AE occurring at any dose that results in any of the following outcomes: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability /incapacity; congenital anomaly / birth defect; medically important event
P. I. Stal, et al. Presented at UEGW. P 1196

37. GIDEON final analysis - the European subset: rate of drug-related AEs by liver disease aetiology
Overview of treatment-emergent AEs according to aetiology of patient’s underlying liver disease %
Hepatitis B
n=201*
Hepatitis C
n=396*
Alcohol use
n=507*
NASH
n=36*
Overall
n=1113*
AEs (all grades)
90.0
85.4
89.2
82.2
83.3
Drug-related AEs (all grades)
67.2
67.9
69.6
63.9
68.8
Serious AEs (all grades)
42.8
42.2
50.9
40.3
46.2
Drug-related serious AEs (all grades)
12.1
7.0
10.8
8.9
10.9
AEs resulting in permanent discontinuation of study drug
29.4
32.8
37.3
36.1
35.1
Treatment-emergent deaths
28.4
22.2
27.4
22.5
25.7
The incidence of AEs (all grades), drug-related Aes (all grades), serious AEs (all grades), and AEs resulting in permanent discontinuation of study drug were comparable in patients with all known underlying aetiologies
*Baseline data collected at study entry, patients may have multiple responses; aDeaths while on treatment or within 30 days of last sorafenib dose
NASH, non-alcoholic steatohepatitis
Ratziu V, et al. Presented at EASL P957

38. Conclusions
In this real-life clinical practice setting, the majority of patients (82.4%) received the recommended initial sorafenib dose of 800 mg/day
Patients on 800 mg/day tended to continue on treatment for longer, have less discontinuations and have a greater median overall survival compared with those patients receiving the lower 400 mg/day dose
Patients treated with ctTACE lived longer than those with no ctTACE. However, it is not clear that this finding is a result of treatment effect or the patients’ selection for ctTACE, due to the limitation and potential bias of an observational study
The incidences of AEs for the 800 mg/day and 400 mg/day sorafenib doses were similar
Adverse event profiles of sorafenib are comparable regardless of history of prior TACE or ctTACE treatment
Daniele B, et al. Presented at ECC P 2581
P. I. Stal, et al. Presented at UEGW. P 1196

39. GIDEON final analysis:
the Italian subset
Overall, 278 patients have been enrolled in Italy between June ‘09 and April ‘11
Salvatore D’A, et al. Presented at EASL P 237

40. GIDEON final analysis - the Italian subset:
baseline patients characteristics
Baseline Factor
n = 274
Age: median (range)
70 (44-90)
Sex: n (%)
Male
227 (82.8)
Female
47 (17.2)
ECOG PS, %
168 (61,3) 1
84 (30,7) 2
20 (7,3)
Missing
2 (0,7)
TNM stage: I
24 (8,8) II
43 (15,7)
IIIa
98 (35,8)
IIIb
3 (1,1)
IIIc
34 (12,4) IV
52 (19)
N/A
BCLC: A
33 (12) B
87 (32) C
142 (52) D
5 (1,5)
N/E
7 (2,5)
Salvatore D’A, et al. Presented at EASL P 237

41. GIDEON final analysis - the Italian subset:
history of of prior treatment by prior TACE and ctTACE
% of n
Prior TACE
n=100
No prior TACE
n=174
Concomitant TACE
n=11*
No concomitant TACE
n=263
Overall
n=274
Surgery 16
14.4
9.1
15.2 15
Locoregional therapy
100
27.5
72.7
52.3
53.6
TACE 35
36.5
RFA 39
18.7
27.3
25.9
HAI 2
0.6
1.1
PEI 17
11.7
13.7
13.5
Other LRTs
0.06 1
0.8
0.7
Systemic therapy a
Other non-systemic therapy b
*Patients in the concomitant TACE groups may also be part of the prior TACE group; aChemotherapy, immunotherapy, or others; bRadiotherapy and other locoregional therapy. HAI, hepatic arterial infusion; LRT, locoregional therapy; PEI, percutaneous ethanol injection; RFA, radiofrequency ablation; TACE, transarterial chemoembolization
Vito L, et al. Presented at EASL P 447

42. GIDEON final analysis - the Italian subset: OS by BCLC
Overall survival
Patients with BCLC stage B had longer OS than BCLC stage C; median OS was not reached for patients with BCLC stage A
Salvatore D’A, et al. Presented at EASL P 237

43. GIDEON final analysis - the Italian subset: OS by ECOG-PS
Overall survival
The majority of patients had an ECOG PS of 0 or 1. Median OS was greater in patients with an ECOG PS of 0 or 1 than in patients with an ECOG PS of 2
Salvatore D’A, et al. Presented at EASL P 237

44. GIDEON final analysis - the Italian subset: OS by TACE
Overall survival
Median OS was greater in patients with prior TACE (697 days, 22.9 months) compared with those who did not receive prior TACE (341 days, 11.2 months)
Vito L, et al. Presented at EASL P 447

45. GIDEON final analysis - the Italian subset: OS by ctTACE
Overall survival
For the small cohort of patients who underwent ctTACE mOS was not reached whilst for those no ctTACE mOS was 383 days
Vito L, et al. Presented at EASL P 447

46. GIDEON final analysis - the Italian subset: rate of treatment-emergent AEs and SAEs by prior TACE and ctTACE %
Prior TACE
n=100
No prior TACE
n=174
Concomitant TACE
n=11*
No concomitant TACE
n=263
Overall
n=274
AEs (all grades) 84
78.9
90.9
84.0
80.8
Drug-related AEs (all grades) 79
59.6
65.8
66.8
Serious Aes a (all grades) 28
32.2
27.3
30.8
30.6
Drug-related serious AEs (all grades) 9
7.6
8.5
8.1
AEs resulting in permanent discontinuation of study drug 37
30.4
18.2
33.5
32.8
The overall incidence of AEs and serious AEs (SAEs) was similar in the prior TACE and no prior TACE populations. The same observation was seen in the ctTACE and no ctTACE populations
*Patients in the concomitant TACE groups may also be part of the prior TACE group; aAny AE occurring at any dose that results in any of the following outcomes: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability / incapacity; congenital anomaly / birth defect; medically important event
Vito L, et al. Presented at EASL P 447

47. Conclusions
The results of the Italian cohort from the GIDEON study are consistent with the global results of the study
Patients treated with prior TACE lived longer than those with no prior TACE possibly because of the earlier stage of disease at initial diagnosis among the first group
Patients treated with ctTACE lived longer than those with no ctTACE. However, due to the small number of patients treated with ctTACE and to the limitation and potential bias of an observational study it is not possible to attribute this difference to a different treatment effect
Adverse event profiles of sorafenib are comparable among the patients with or without prior TACE and ct TACE. Potential differences among those receiving or not ctTACE might be caused by the small number of patients in the ctTACE group
Salvatore D’A, et al. Presented at EASL P 237
Vito L, et al. Presented at EASL P 447