Radiol Oncol 2020; 54(2): 233-236. doi: 10.2478/raon-2020-0027
233
research article
Sorafenib for the treatment of hepatocellular 
carcinoma: a single-centre real-world study
Jurij Hanzel1, Tajda Kosir Bozic1, Borut Stabuc1,2, Rado Jansa1,2
1 Department of Gastroenterology, University Medical Centre Ljubljana, Ljubljana, Slovenia
2 Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
Radiol Oncol 2020; 54(2): 233-236.
Received 18 November 2019
Accepted 1 December 2019
Correspondence to: Rado Janša, Ph.D., M.D., Department of Gastroenterology, University Medical Centre Ljubljana, Japljeva ulica 2, 
SI-1000 Ljubljana, Slovenia. E–mail: rado.jansa@kclj.si
Disclosure: No potential conflicts of interest were disclosed. 
Background. Sorafenib is an oral multi-kinase inhibitor used for the treatment of hepatocellular carcinoma. Its effica-
cy in randomised controlled trials was demonstrated in patients with well-preserved liver function and good functional 
status. In the real-world setting, treatment is often offered to patients outside these criteria. We therefore performed a 
single-centre real-world cohort study on the efficacy of sorafenib in patients with hepatocellular carcinoma.
Patients and methods. We identified all patients with hepatocellular carcinoma initiating treatment with sorafenib 
between January 2015 and January 2018. The primary endpoint was overall survival (OS) since starting sorafenib. 
Clinical and demographic variables associated with survival were studied.
Results. The median OS was 13.4 months (95% CI 8.2–18.6). Multivariable Cox’s regression identified worse ECOG per-
formance status (HR 2.21; 95% CI 1.56–3.16; P < 0.0001), Child-Pugh class C (HR 52.4; 95% CI 3.20–859; P = 0.005) and ab-
sence of prior locoregional treatment (HR 2.30; 95% CI 1.37–3.86; P = 0.002) to be associated with increased mortality. 
Conclusions. Careful selection of patients for treatment with sorafenib is of paramount importance to optimize 
outcomes.
Key words: survival; multivariable analysis; real-world cohort study
Introduction
Sorafenib is an oral multi-kinase inhibitor, which 
inhibits tumours angiogenesis through inhibition 
of vascular endothelial growth factor (VEGF) and 
platelet-derived growth factor (PDGF) signalling 
pathways. It has demonstrated a significant pro-
longation in overall survival of patients with ad-
vanced-stage hepatocellular carcinoma (HCC) up 
to 2.8 months.1,2 The two landmark trials included 
mainly patients with compensated liver cirrhosis 
of viral aetiology and an excellent baseline func-
tional status. Consequently, sorafenib is formally 
indicated only in patients with well-preserved liver 
function (Child-Pugh A) and advanced tumours 
(Barcelona Clinic Liver Cancer [BCLC] C) or inter-
mediate stage tumours (BCLC B) progressing after 
locoregional therapy.3
Nevertheless, sorafenib is often used outside 
these criteria in the real-world setting, mainly due 
to the absence of alternative treatment options. As 
these patient subgroups were not studied in regis-
trational trials, only large observational non-rand-
omized cohort studies can help inform practice.4-6
We therefore a retrospective real-world cohort 
study of patients treated with sorafenib for ad-
vanced HCC, investigating its efficacy and vari-
ables associated with OS. 
Patients and methods
Patients and study design
We performed a retrospective cohort study of 
all patients with HCC initiating treatment with 
sorafenib between January 2015 and January 2018, 
Radiol Oncol 2020; 54(2): 233-236.
Hanzel J et al. / Sorafenib in HCC – single-centre real-world experience234
who were followed until October 2018 at a single 
tertiary centre. Data collection was approved by 
the institutional ethics committee, while treatment 
did not differ from the standard of care and thus 
did not require additional approval.
We included all consecutive patients aged at 
least 18 years with a histologically or radiologically 
confirmed diagnosis of HCC, who were treated 
with sorafenib. The decision for initiation of the 
drug was made based on the consensus of the Liver 
Multidisciplinary Team. Patient records were ret-
rospectively reviewed for demographic and clini-
cal information. The date of death was extracted 
from the national health insurance database.
The primary outcome was OS from initiation of 
sorafenib. We explored the relationship of clinical 
characteristics with OS.
Statistical analysis
Continuous variables are given as medians with 
interquartile ranges (IQR). Univariable associa-
tion analyses with survival were performed us-
ing the Kaplan-Meier method with log-rank test-
ing. Multivariable analysis was performed using 
a Cox-proportional hazards model with stepwise 
backward selection where variables were removed 
if they did not achieve statistical significance at P 
< 0.05. All analyses were performed on an inten-
tion-to-treat basis. Analyses were performed using 
SPSS, Version 25 (IBM, Chicago, USA).
Results
Patient characteristics
We included 115 patients, who were predominant-
ly male with Child-Pugh class A alcoholic cirrhosis 
with good performance status (Table 1).
Survival outcomes
A total of 83 patients (72%) died during the study 
period. The median OS since initiation of sorafenib 
was 13.4 months (95% CI 8.2–18.6).
In univariable analysis, reduced OS was asso-
ciated with worse ECOG performance status (P < 
0.0001), higher Child-Pugh class (P < 0.0001), high-
er baseline AFP (P = 0.003) and absence of prior 
locoregional treatment (P < 0.0001) (Table 2). The 
associations of liver disease aetiology (P = 0.192), 
BCLC stage (P = 0.539), gender (P = 0.944) and age 
at treatment initiation (P = 0.201) with OS were not 
statistically significant.
Multivariable analysis demonstrated significant 
associations between mortality and ECOG per-
formance status (HR 2.21; 95% CI 1.56–3.16; P < 
0.0001), Child-Pugh class C (HR 52.4; 95% CI 3.20–
859; P = 0.005) and absence of prior locoregional 
treatment (HR 2.30; 95% CI 1.37–3.86; P = 0.002), 
but not baseline AFP (HR 1.00; 95% CI 0.8–1.2; P = 
0.278) (Table 2, Figure 1).
Discussion 
HCC is among the leading causes of cancer-related 
deaths. It primarily develops from cirrhosis, and 
many patients are infected with hepatitis C virus 
(HCV) or hepatitis B virus (HBV). Treatment with 
the multikinase inhibitor sorafenib is a systemic 
therapy option for patients with advanced HCC 
since 2008.
TABLE 1. Patient characteristics at initiation of sorafenib (n = 
115)
Variable
Male gender, n (%) 96 (84)
Age, years, median (IQR) 67 (60–72)
ECOG performance status
0
1
2
3
31 (27)
47 (40.9)
36 (31.3)
1 (0.9)
Aetiology of underlying liver disease, n (%)
Alcoholic liver disease
Hepatitis B
Hepatitis C
Non-alcoholic steatohepatitis
Cryptogenic
Wilson’s disease
Primary biliary cholangitis
HCC in non-cirrhotic liver
56 (49)
11 (9.6)
7 (6.1)
18 (15.7)
10 (8.7)
1 (0.9)
1 (0.9)
11 (9.6)
Child-Pugh class, n (%)
A
B
C
77 (66.9)
37 (32.2)
1 (0.9)
BCLC stage, n (%)
A
B
C
3 (2.6)
42 (36.5)
70 (60.9)
Prior treatment, n (%) 45 (39.1)
Resection
RFA
Transplant
TACE
Radioembolization
10 (8.7)
2 (1.8)
3 (2.6)
29 (25.2)
5 (4.3)
AFP, kU/L, median (IQR) 6–1518)
AFP = alpha-fetoprotein; BCLC = Barcelona Clinic Liver Cancer; ECOG = 
Eastern Cooperative Oncology Group; HCC = hepatocellular carcinoma; 
IQR = interquartile range; RFA = radiofrequency ablation; TACE = trans-
arterial chemoembolization
Radiol Oncol 2020; 54(2): 233-236.
Hanzel J et al. / Sorafenib in HCC – single-centre real-world experience 235
Systemic therapy has helped prolong survival 
after disease progression. Clinical management of 
patients should target improvement of patient OS. 
Sorafenib therapy is recommended in guidelines as 
the first-line option in patients who cannot benefit 
from resection, transplantation, ablation or TACE, 
and still have preserved liver function and signifi-
cantly prolonged OS and TTP. 
Sorafenib monotherapy remains the standard 
of care in unresectable HCC. Sorafenib has dem-
onstrated survival benefit in patients with unre-
sectable HCC in two (2) randomized, placebo-con-
FIGURE 1. Kaplan-Meier plots of overall survival (OS) after initiating sorafenib stratified by (A) ECOG performance status, (B) Child-Pugh class, and 
(C) prior locoregional treatment.
TABLE 2. Factors associated with overall survival (OS) after initiation of sorafenib
Univariable analysis Multivariable analysis
Median survival in 
months (95% CI) Log rank P value
Hazard ratio (95% 
CI)
Cox’s regression P 
value
ECOG performance status
    0
    1
    2
    3
25.1 (12.8–37.4)
17.0 (7.0–26.9)
5.5 (3.7–7.3)
7.3 (/)
<0.0001 2.21 (1.56–3.16) <0.0001
Child-Pugh class
    A
    B
    C
16.9 (12.8–21.0)
6.7 (4.7–8.7)
1.0 (/)
<0.0001 1.001.34 (0.80–2.26)
52.4 (3.20–859)
0.271
0.005
Baseline AFP
    < 200
    ≥ 200
17.0 (9.3–24.6)
6.7 (5.6–7.8)
0.003 1.00 (0.8–1.2) 0.278
Prior locoregional treatment
    Yes
    No
24.0 (20.1–27.9)
7.3 (5.0–9.5)
<0.0001 1.00
2.30 (1.37–3.86) 0.002
Liver disease aetiology
    Alcoholic
    Other
8.6 (3.80–13.3)
16.7 (13.5–19.9)
0.192
BCLC stage
    A
    B
    C
22.4 (7.0–37.7)
14.5 (5.1–23.9)
13.4 (7.1–19.7)
0.539
Gender
    Female
    Male
8.8 (7.0–10.7)
13.8 (10.1–17.6)
0.944
Age
    < 70 years
    ≥ 70 years
15.0 (11.2–18.8)
8.4 (6.0–10.8)
0.201
AFP = alpha-fetoprotein; BCLC = Barcelona Clinic Liver Cancer; ECOG = Eastern Cooperative Oncology Group; IQR = interquartile range
A B C
Radiol Oncol 2020; 54(2): 233-236.
Hanzel J et al. / Sorafenib in HCC – single-centre real-world experience236
trolled, double-blind, phase III trials: SHARP and 
AP. The use of sorafenib significantly increased 
OS: 10.7 months vs. 7.9 months (SHARP study) and 
radiologic progression was significantly lower in 
the sorafenib group of patients.8
The use of Sorafenib also significantly increased 
OS in Asian-Pacific study. However, the results 
compared with SHARP study were worst espe-
cially because of different demographic character-
istics of patients, more extrahepatic spread, greater 
number of hepatic tumor lesions and poorer ECOG 
performance status.
In GIDEON, real life analysis of the sorafenib 
group of patients median OS was 8.6 month vs. 10.4 
in SHARP study. Clinical outcomes of advanced 
HCC patients treated with sorafenib in real-life 
practice are better compared to the other studies 
conducted in the Asia-Pacific region in terms of 
survival and tolerability. Extrahepatic spread and 
combination with other therapies are of predictive 
value for OS of advanced HCC. Further studies 
are required to maximize the effect of sorafenib in 
combination with other modalities.7,8
In our retrospective study, we collected and 
analyzed the clinical outcomes of advanced HCC 
patients who underwent treatment with sorafenib 
in real-life clinical setting. We found that HCC pa-
tients with Child-Pugh A exhibited a significantly 
higher median survival. In the present study, fac-
tors that are predictive of OS in HCC patient treat-
ed with sorafenib include gender, extrahepatic 
spread, and combined other therapies.7,8
In the Slovenian study, HCC patients treated 
with sorafenib had median OS of 13.4 months, 
which is longer than that reported in SHARP (10.5 
months) and GIDEON (Global Investigation of 
Therapeutic Decisions in HCC and of its treatment 
with sorafenib) (10.8 months).
Multivariable analysis of the Slovenian group 
of patients demonstrated significant associations 
between mortality and ECOG performance status, 
Child-Pugh class C and absence of prior locore-
gional treatment, but not baseline AFP.
There are several limitations in this retrospec-
tive designed analysis. Being a retrospective study, 
it is difficult to ascertain the actual cause of death 
in our cohort. The population size examined in 
our study is relatively small, which may limit the 
statistical power. Small population size may have 
influences on subgroup analysis. Other limitations 
include the reduced initial dose of sorafenib based 
on clinical decision made by individual physicians 
and adjustment of dosages during treatment due 
to intolerance. 
However, our results are comparable with re-
sults of other worldwide studies.
In conclusions, careful selection of patients for 
sorafenib treatment is important. Treatment of 
HCC patients should be performed in experienced 
centers, where the decision of treatment of each pa-
tients should be made after previous presentation 
of patients at multidisciplinary board of experts.
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