Development of systemic therapy for hepatocellular carcinoma at 2013: Updates and insights

Table 1 Results of completed phase III clinical trial on systemic agents for hepatocellular carcinoma

Clinical trial	Drug	Population	TTP (mo)	OS (mo)
1st line
SHARP[89]	Sorafenib	19% HBV; 29% HCV	5.5	10.7
	Placebo	18% HBV; 27% HCV	2.8 (P < 0.001)	7.9 (P < 0.001)
Asian SHARP[90]	Sorafenib	71% HBV; 11% HCV	2.8	6.5
	Placebo	78% HBV; 4.0% HCV	1.4	4.2 (P = 0.014)
SUN1170[1]	Sunitinib	55% HBV; 21% HCV	4.1	8.1
	Sorafenib	53% HBV; 22% HCV	3.8 (P = 0.1688)	10.0 (P = 0.0019)
BRISK-FL[2]	Brivanib	44% HBV; 20% HCV	4.2	9.5
	Sorafenib	45% HBV; 21% HCV	4.1 (P = 0.85)	9.9 (P = 0.37)
Linifanib vs sorafenib[12]	Linifanib	49% HBV	5.4	9.1
	Sorafenib		4.0 (P = 0.001)	9.8 (P = NS)
SEARCH[57]	Sorafenib + Erlotinib	NA	3.2	9.5
	Sorafenib		4.0 (P = 0.91)	8.5 (P = 0.2)
Chemotherapy[62]	Doxorubicin	80% HBV; 8% HCV	NA	6.8
	PIAF	82% HBV; 4% HCV		8.7 (P = 0.83)
2nd line
BRISK-PS[3]	Brivanib	NA	4.2	9.4
	Placebo		2.7 (P = 0.0001)	8.2 (P = 0.33)

HBV: Hepatitis B virus; HCV: Hepatitis C virus; NA: Not available; OS: Overall survival; TTP: Time to progression; NS: Non-significant; HCC: Hepatocellular carcinoma.

Table 2 List of selected ongoing clinical trials on novel targeted therapy for hepatocellular carcinoma

Drug	Design	Phase	Status	NCT number
Single-agent
TKI
Dovitinib (TKI258)	Dovitinib vs sorafenib (1st line)	Randomized phase II	Compl-eted	NCT01232296
Carbo- zantinib	Carbozantinib vs placebo (2nd line)	Phase III	Ongoing	NCT01908426
c-MET inhibitor
Tivantinib	Tivantinib vs placebo (2nd line)	Phase III	Ongoing	NCT01755767
INC280	INC280 (1st line in c-MET expressing HCC)	Phase I/II	Ongoing	NCT01737827
Oncolytic poxvirus
JX594	JX594 vs placebo (2nd line)	Randomized phase II	Ongoing	NCT01387555
Glypican-3
GC33	GC33 vs placebo (2nd line)	Phase III	Compl-eted	NCT01507168
mTOR inhibitor
Everolimus	Everolimus vs placebo (2nd line)	Phase III	Press release	NCT01035229
Temsir- olimus	Temsirolimus (1st or 2nd line)	Phase II	Abstract	NCT01251458
CC-223	CC-223 in solid tumors including HCC	Phase I/II	Ongoing	NCT01177397
Arginine deprivation therapy
ADI-PEG 20	ADI-PEG 20 vs placebo (2nd line)	Phase III	Ongoing	NCT01287585
Combination
Sorafenib	Sorafenib + doxorubicin vs sorafenib	Phase III	Accrual	NCT01015833
Sorafenib	TACE + sorafenib vs TACE (ECOG 1208)	Phase III	Accrual	NCT01004978
Everolimus	TACE + everolimus vs TACE	Randomized phase II	Accrual	NCT01379521
Axitinib	TACE + axitinib	Phase II	Accrual	NCT01352728
Bevacizumab and Erlotinib	Bevacizumab + erlotinib vs sorafenib	Randomized phase II	Accrual	NCT01180959

TACE: Transarterial chemoembolization; TKI: Tyrosine kinase inhibitor; HCC: Hepatocellular carcinoma; c-MET: c-mesenchymal-epithelial transition factor-1.