Hepatocellular carcinoma: Will novel targeted drugs really impact the next future?

Table 1 On-going National Cancer Institute-sponsored phase III trials

Target molecule	Molecule	trial	Phase	Details	Locoregional treatment	Primary outcome	Estimated enrollment	Start date	Estimated study completion date	Ref.
VEGFR	Ramucirumab	Ramucirumab (LY3009806) vs placebo in participants with hepatocellular carcinoma and elevated baseline alpha-fetoprotein (REACH-2)	III	CPA, BCLC Stage C disease or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy, Prior sorafenib treatment		OS	399 pts	July 2015	April 2018	NCT02435433
VEGF	Sorafenib	TACE with or without Sorafenib	III	CPA or B7, first line treatment, branch not main PVI	Y	PFS	400 pts	October 2009	February 2018	NCT01004978
	Sorafenib	A randomized, controlled phase III trial of sorafenib with or without conventional TACE in patients with advanced HCC (STAH Study)	III	CPA or B7		OS	338 pts	February 2013	October 2017	NCT01829035
	Regorafenib	Study of regorafenib after sorafenib in patients with hepatocellular carcinoma (RESORCE)	III	CPA		OS	573 pts	May 2013	October 2016	NCT01774344
VEGF, FGF, PDGF, RET,KIT	Lenvatinib	A multicenter, open-label, phase 3 trial to compare the efficacy and safety of lenvatinib (E7080) vs sorafenib in first-line treatment of subjects with unresectable hepatocellular carcinoma	III	CPA, BCLC Stage B or C		OS	954 pts	March 2013	April 2016	NCT01761266
MET, RET, VEGF	Cabozantinib (XL 184)	Randomized controlled trial of XL184 vs placebo after sorafenib (CELESTIAL)	III	CPA		OS	760 pts	August 2013	October 2016	NCT01908426
MET	Tivantinib (ARQ197)	Study of tivantinib in subjects with inoperable hepatocellular carcinoma who have been treated with one prior therapy (METIV-HCC)	III	MET Diagnostic-High tissue		OS	368 pts	December 2012	June 2017	NCT01755767
	Tivantinib (ARQ197)	A randomized double-blind, placebo-controlled Japanese phase III trial of ARQ 197 in hepatocellular carcinoma (HCC) (JET-HCC)	III	c-Met high in tumor sample, CPA		PFS	160 pts	January 2014	December 2016	NCT02029157
PD-1	Nivolumab	First line treatment with nivolumab vs sorafenib (CheckMate 459: CHECKpoint pathway and nivoluMAb clinical trial evaluation 459)	III	CPA		TTP, OS	726 pts	November 2015	June 2019	NCT02576509
PD-1	Pembrolizumab	Study of pembrolizumab (MK-3475) vs best supportive care in participants with previously Systemically treated advanced hepatocellular carcinoma (MK-3475-240/KEYNOTE-240)	III	CPA, BCLC Stage C disease or BCLC Stage B disease not amenable to locoregional therapy		PFS, OS	408 pts	April 2016	April 2018	NCT02702401

PFS: Progression free survival; TTP: Time to progression; ORR: Overall response rate; OS: Overall survival; VEGF: Vascular endothelial growth factor; PDGF: Platelet derived growth factor; FGF: Fibroblast derived growth factor; PD-1: Programmed death-1; CP: Child-Pugh class; BCLC: Barcelona Clinic Liver Cancer; PVI: Portal vein invasion; TACE: Transarterial chemoembolization.