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Gomaa et al. Advanced HCC: current and potential therapies

placebo (SATURNE) (NCT01164202) is ongoing. A phase III RCT of Selective Internal Radiation Therapy
(SIRT) versus sorafenib in advanced HCC (SIRveNIB)
Hepatic arterial infusion chemotherapy is ongoing (NCT01135056). A study evaluating the
The Japanese Society of Hepatology and the Korean monoclonal antibody to PD-1 receptor nivolumab in
National Cancer Center both recommend hepatic combination with TARE is under way (NCT02837029).
arterial infusion chemotherapy (HAIC) in their RCTs are ongoing to define the role of TARE as first-
guidelines for management of patients with advanced line or second-line therapy in advanced HCC.
HCC and vascular invasion. [69,80,81]
CONCLUSION
In a single-center study in Japan, the HAIC using
5-fluorouracil and pegylated interferon α2b was Sorafenib is still the only approved front-line therapy,
investigated compared to sorafenib for treatment of and several needs are still unmet and need to be
advanced HCC. The early ORR was higher in the addressed: the combination of local with systemic
HAIC group than in the sorafenib group (71.4% vs. therapies, the optimal timing of molecular targeted
10.5%, P < 0.01). The 18-month survival rate was agents in relation to loco-regional treatment, the
55.6% vs. 16.2%, P = 0.03 for the HAIC and sorafenib combinations of systemic targeted therapies, and
groups respectively. [82] second-line therapies. Results of recent trials point
to several promising therapeutic options: lenvatinib
A multi-center study that included 110 patients with as front-line therapy, and regorafenib and nivolumab
advanced HCC found that HAIC using cisplatin and as second-line therapy. Several other molecules and
5-fluorouracil with or without epirubicin, demonstrated combinations are in early stages of development,
higher treatment response rate (24% vs. 13.3%) and and more effective therapies will evolve over the next
a better median OS (7.1 vs. 5.5 months) compared few years. However, improving screening and early
to sorafenib. [83] A RCT is recruiting to elucidate the detection, and improving access to therapy in limited
efficacy of HAIC of FOLFOX compared to sorafenib in resource settings are as important in improving global
treatment of advanced HCC (NCT02774187). A phase outcome of HCC.
III randomized open label clinical trial to investigate the
efficacy and safety of HAIC (using FOLFOX) compared Authors’ contributions
with TACE in patients with HCC with major portal Reviewed the literature and wrote the manuscript: A.
venous tumor thrombus is recruiting (NCT02856126). Gomaa, I. Waked

The efficacy and safety of HAIC with cisplatin and Financial support and sponsorship
5-fluorouracil in patients who have progressed or None.
were intolerant to sorafenib with non-metastatic HCC
is being evaluated further, stratified by expression of Conflict of interest
biomarker predicting therapeutic response is ongoing
(the SHINE study, NCT02967887). There are no conflicts of interest.

Radioembolisation Patient consent
Trans-arterial radio-embolization (TARE) using Not applicable.
Yttrium-90 spheres is well tolerated with survival rates
reported similar to TACE with fewer side effects, better Ethics approval
response rate and longer time to progression. [4,84-86] Not applicable.
TARE is as safe and effective as sorafenib in
advanced-stage HCC. [4,87-90] The median survival with Supplementary materials
TARE was 13.8 months compared to 10 months with 1. Supplementary Tables 1-4
sorafenib (P > 0.05), and complete response was only 2. Supplementary References 1-24
observed in 6.3% of patients in the TARE group. [91]
TARE alone or combined with sorafenib vs. sorafenib
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118 Hepatoma Research ¦ Volume 3 ¦ June 15, 2017