Transcript Global Investigation of therapeutic DEcisions

Global Investigation of therapeutic
DEcisions in
hepatocellular carcinoma and Of its
treatment with sorafeNib (GIDEON) study
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: http://www.nccn.org/ Accessed May 29,2014. 2. EASL–EORTC Clinical Practice Guidelines: Management of
hepatocellular carcinoma Journal of Hepatology 2012 vol. 56 j 908–943 Available on: http://www.easl.eu/assets/application/files/d38c7689f123edf_file.pdf . 3. Position
paper AISF DLD 2013 45(2013) 712-723. 4. AIOM Guidelines. Available at: http://www.aiom.it/ 5. Llovet JM, et al. N Engl J Med. 2008;359(4):378-390. 6. Cheng AL, et
al. Lancet Oncol. 2009;10(1):25-34. 7. Lencioni R, et al. Int J Clin Prac. 2010;64(8):1034-1041.
8. Marrero JA et al. Abstract presented at AASLD 2011 Annual Meeting
The GIDEON study: design and objectives
The GIDEON study is a large, global, prospective, noninterventional 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):1034-1041.
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):1034-1041.
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
The GIDEON study: safety, efficacy, treatment and
baseline patient assessments and end-points
Safety
Efficacy
Treatment for HCC
• Adverse events
• OS
• TTS
• PFS
• RR
• SD
• Sorafenib therapy
• Duration of treatment
• Relation
• Seriousness
• NCI-CTC grade
• Action taken
• Outcome
• Child-Pugh score
• ECOG PS
• 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
•ECOG PS
•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
The GIDEON study:
timeline and planned analyses
2008-2009
2010
Phase I
Objectives:
Phase II
Objectives:
Phase III
Objectives:
Phase IV and V
Objectives:
• Site initiation
• Study initiation
• Safety assessment in
Child-Pugh B
• First interim analysis
(500 patients)
• Second interim
analysis (1500 patients)
• Safety assessment in
Child-Pugh B
• 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
Lencioni R et al. Int J Clin Pract 2010;64:1034–41
2011-2012
2013-2015
- Safety
- Efficacy
• Provide data to
regolatory organizations
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)
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)
GIDEON final analysis:
baseline patients characteristics by CP status
% of n
Child-Pugh A Child-Pugh B Child-Pugh C
(n=1968)
(n=666)
(n=74)
total
(n=3202)*
Number of patients
615
208
23
100
Male/female
Median age, years
ECOG PS
0 or 1
>2
TNM stage
I
II
III
IV
BCLC stage
A
B
C
82/18
64
81/19
61
82/18
58
82/18
62
88
7
72
21
59
34
83
12
5
15
36
36
4
9
43
33
7
14
34
30
5
12
35
35
8
22
57
6
20
56
0
0
1
7
20
52
3
5
89
5
D
*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)
GIDEON final analysis:
overall treatment-emergent safety data by CP status
% of n
Child-Pugh A Child-Pugh B Child-Pugh C
(n=1968)
(n=666)
(n=74)
total
(n=3202)a
84
88.6
91.9
85.3
68.5
36.0
64.4
60.4
39.2
70.3
66.0
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
AEs (all grades)
Drug-related AEs (all grades)
Serious AEsb (all grades)
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)
GIDEON final analysis:
rate of drug-related AEsa by CP status
Rate, event per
patient-yeara
aRate
Child-Pugh A Child-Pugh B
(n=1968)
(n=666)
Child-Pugh C
(n=74)
Total
(n=3202)b
Any AE
1.17
25.5
1.41
1.24
Diarrhea
0.48
25.5
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
0.21
Anorexia
0.18
7.4
0.24
0.18
Nausea
0.09
6.2
0.34
0.12
Pain, abdomen,
NOS
0.05
3.6
0.19
0.06
Liver dysfunction
0.03
3.6
0
0.03
calculation based on treatment-emergent AEs with >10% incidence and 365.25 days per year; bIncludes 493 non-evaluable patients
Marrero J, et al. J Clin Oncol 31, 2013 (suppl; abstr 4126)
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)
GIDEON final analysis:
sorafenib dosing and treatment duration by CP status
Child-Pugh A Child-Pugh B Child-Pugh C
total
(n=1968)
(n=666)
(n=74)
(n=3202)a
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
Initial dose of 800 mg, % of



aIncludes
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
493 non-evaluable patients
Marrero J, et al. J Clin Oncol 31, 2013 (suppl; abstr 4126)
GIDEON final analysis:
duration of sorafenib treatment by CP status
Duration of sorafenib treatment
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)
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)
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)
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 2013. P 2594
GIDEON final analysis:
TTP by BCLC stage
Time to progression
Bronovicki J-P, et al. Presented at ECC 2013. P 2594
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 2013. P 2594
GIDEON final analysis:
TTP by TNM stage
Time to progression
TNM, tumor node metastasis
Bronovicki J-P, et al. Presented at ECC 2013. P 2594
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 2013. P 2594
GIDEON final analysis:
TTP by ECOG performance status
Time to progression
Bronovicki J-P, et al. Presented at ECC 2013. P 2594
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)
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 2013. P 2581
GIDEON final analysis - the European subset:
baseline patients characteristics by initial dose
% of n
Male
Median age, years (range)
Etiology of underlying
liver disease, %a
Hepatitis B
Hepatitis C
Alcohol use
NASH
Unknown
ECOG PS, %
0
1
2
3
4
Unknown
aBaseline
400 mg/day
(n=171)
800 mg/day
(n=917)
Overall
(n=1113)
84.8
83.6
83.3
69.0 (15–90)
66.0 (19–94)
66.0 (15–94)
18.7
36.3
30.4
2.9
17.0
18.2
34.8
35.1
3.4
17.6
18.1
35.6
34.3
3.2
17.2
31.6
45.0
12.9
5.3
0
5.3
47.4
38.4
9.6
1.1
0.1
3.4
45.4
39.2
10.1
1.7
<0.1
3.6
data collected at study entry, patients may have multiple responses;
Daniele B, et al. Presented at ECC 2013. P 2581
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)
58.5
25.7
1.8
14.0
66.0
18.8
1.0
14.3
64.8
19.9
1.1
14.3
10.5
23.4
40.9
18.7
0.6
7.5
24.3
55.9
8.3
0.2
8.5
24.3
52.9
10.0
0.3
Child-Pugh status, %b
A
B
C
Not evaluablec
BCLC stage, %b
A
B
C
Not evaluable/unknownd
Missinge
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
bAt
Daniele B, et al. Presented at ECC 2013. P 2581
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)
6.4
13.5
34.5
1.8
8.2
20.5
14.6
4.7
10.8
30.4
2.4
11.6
28.7
11.3
5.6
11.1
31.1
2.3
10.9
27.2
11.7
TNM stage, %b
I
II
IIIa
IIIb
IIIc
IV
Not evaluablec
Time from initial diagnosis
to start of sorafenib therapy
Number of patients with
available data
Median, months
bAt
140 (81.8%)
782 (85.3%)
941 (84.6%)
2.84
3.83
3.72
study entry; cNecessary data for scoring were not collected in investigators’ routine practice
Daniele B, et al. Presented at ECC 2013. P 2581
GIDEON final analysis - the European subset:
history of of prior treatment by prior TACE and ctTACE
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
15.5
Locoregional
therapy
100
15.6
78.8
41.8
43.5
100
26.4
1.6
8.2
1.4
3.5
0
9.3
0.7
3.9
1.1
3.9
73.1
17.3
0
3.8
1.9
1.9
34.1
14.8
1.0
5.4
1.1
1.1
33.1
14.9
1.0
5.3
1.2
3.8
1.1
1.1
1.9
3.9
1.2
% of n
TACE
RFA
HAI
PEI
Other LRTs
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 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
GIDEON final analysis - the European subset:
duration of sorafenib treatment by initial dose
Duration of sorafenib treatment

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 2013. P 2581
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 2013. P 2581
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
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
1.0
0.9
Survival distribution function
Survival distribution function
1.0
11.7 months (358 days)
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0
200
400
600
800
1000
1200
Time since start of treatment (days)
0.9
14.2 months (432 days)
0.8
0.7
0.6
0.5
0.4
0.3
0
200
400
600
800
1000
1200
Time since start of treatment (days)
Overall survival according to
alcohol use
Survival distribution function
1.0
0.9
0.8
12.9 months (394 days)
0.7
0.6
0.5
0.4
0.3
0.2
0
200
400
600
800
1000
Time since start of treatment (days)
Ratziu V, et al. Presented at EASL 2014. P957
1200
While a small advantage in OS
was reported for patients with
hepatitis C, TTP was comparable
for each of the underlying
aetiologies
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 2014. P957
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
68.8
Serious Aes a (all grades)
57.3
44.5
46.2
Drug-related serious AEs (all
grades)
11.1
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 2013. P 2581
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
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
Treatmentemergent 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 2014. P957
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 2013. P 2581
P. I. Stal, et al. Presented at UEGW. P 1196
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 2014. P 237
GIDEON final analysis - the Italian subset:
baseline patients characteristics
Baseline Factor
Age: median (range)
Sex: n (%)
Male
Female
ECOG PS, %
0
1
2
Missing
TNM stage:
I
II
IIIa
IIIb
IIIc
IV
N/A
BCLC:
A
B
C
D
N/E
Salvatore D’A, et al. Presented at EASL 2014. P 237
n = 274
70 (44-90)
227 (82.8)
47 (17.2)
168 (61,3)
84 (30,7)
20 (7,3)
2 (0,7)
24 (8,8)
43 (15,7)
98 (35,8)
3 (1,1)
34 (12,4)
52 (19)
20 (7,3)
33 (12)
87 (32)
142 (52)
5 (1,5)
7 (2,5)
GIDEON final analysis - the Italian subset:
history of of prior treatment 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
Surgery
16
14.4
9.1
15.2
15
Locoregional
therapy
100
27.5
72.7
52.3
53.6
100
39
2
17
0.06
1
0
18.7
0.6
11.7
1
0.6
72.7
27.3
0
9.1
0
0.8
35
25.9
1.1
13.7
0.8
0
36.5
25.9
1.1
13.5
0.7
0.7
2
0.6
9.1
0.8
1.1
% of n
TACE
RFA
HAI
PEI
Other LRTs
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 2014. P 447
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 2014. P 237
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 2014. P 237
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 2014. P 447
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 2014. P 447
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
90.9
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
0
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 2014. P 447
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 2014. P 237
Vito L, et al. Presented at EASL 2014. P 447