Targeted and immune therapies for hepatocellular carcinoma: Predictions for 2019 and beyond

Table 1 Phase III clinical trials of advanced stage hepatocellular carcinoma

Target population		Design	Trial name	Result	Presentation	Publication	1st author
Advanced	First line	1 Sorafenib vs Sunitinib	SUN1170	Negative	ASCO 2011	JCO 2013[6]	Cheng AL
		2 Sorafenib +/- Erlotinib	SEARCH	Negative	ESMO 2012	JCO 2015[7]	Zhu AX
		3 Sorafenib vs Brivanib	BRISK-FL	Negative	AASLD 2012	JCO 2013[8]	Johnson PJ
		4 Sorafenib vs Linifanib	LiGHT	Negative	ASCO-GI 2013	JCO 2015[9]	Cainap C
		5 Sorafenib +/- Doxorubicin	CALGB 80802	Negative	ASCO-GI 2016
		6 Sorafenib +/- HAIC	SILIUS	Negative	EASL 2016	Lancet GH 2018[10]	Kudo M
		7 Sorafenib +/- Y90	SARAH	Negative	EASL 2017	Lancet-O 2017[11]	Vilgrain V
		8 Sorafenib +/- Y90	SIRveNIB	Negative	ASCO 2017	JCO 2018[12]	Chow P
		9 Sorafenib vs Lenvatinib	REFLECT	Positive	ASCO 2017	Lancet 2018[34]	Kudo M
		10 Sorafenib vs Nivolumab	CheckMate-459	Ongoing
		11 Sorafenib vs Durvalumab + Tremelimumab vs Durva	HIMALAYA	Ongoing
		12 Sorafenib vs Atezolizumab + Bevacizumab	Imbrave 150	Ongoing
		13 Sorafenib vs Tislelizumab		Ongoing
	Second line	1 Brivanib vs Placebo	BRISK-PS	Negative	EASL 2012	JCO 2013[13]	Llovet JM
		2 Everolimus vs Placebo	EVOLVE-1	Negative	ASCO-GI 2014	JAMA 2014[14]	Zhu AX
		3 Ramucirumab vs Placebo	REACH	Negative	ESMO 2014	Lancet-O 2015[15]	Zhu AX
		4 S-1 vs Placebo	S-CUBE	Negative	ASCO 2015	Lancet GH 2017[16]	Kudo M
		5 ADI-PEG 20 vs Placebo	NA	Negative	ASCO 2016	Ann Oncol 2018[17]	Abou-Alfa G
		6 Regorafenib vs Placebo	RESORCE	Positive	WCGC 2016	Lancet 2017[41]	Bruix J
		7 Tivantinib vs Placebo	METIV-HCC	Negative	ASCO 2017	Lancet-O 2018[18]	Rimassa L
		8 Tivantinib vs Placebo	JET-HCC	Negative	ESMO 2017
		9 DT vs Placebo	ReLive	Negative	ILCA 2017
		10 Cabozantinib vs Placebo	CELESTIAL	Positive	ASCO-GI 2018	NEJM 2018[45]	Abou-Alfe G
		11 Ramucirumab vs Placebo	REACH-2	Positive	ASCO 2018	Lancet-O 2019[30]	Zhu AX
		12 Pembrolizumab vs Placebo	KEYNOTE-240	Negative

HAIC: Hepatic arterial infusion chemotherapy; Doxorubicin-loaded nanoparticles.