Chemotherapy for hepatocellular carcinoma: The present and the future

Table 1 Targeted drugs under evaluation in advanced hepatocellular carcinoma

Drug	Molecular target	Study design	DCR	PFS	OS	TTP	Tolerabilty	Phase III study
Lenvatinib[46]	VEGFR, FGFR, PDGFR,RET, KIT	Phase I/II (first line)	NR	NR	18.7 mo	12.8 mo	Favorable profile	Ongoing (E7080)
Cabozantinib[47]	VEGFR-2, MET, RET	Phase II (second line)	68% at 12 wk	4.2 mo	NR	NR	Favorable profile	Ongoing (NCT01908426 – CELESTIAL)
Tivantinib[48]	c-MET	Phase II (vs placebo, second line)	MET low NS MET high 50% vs 20%	NR	MET low NS MET high 7.2 mo vs 3.8 mo; P = 0.01	MET low NS MET high 2.7 mo vs 1.4 mo; P = 0.04	Severe neutropenia	Ongoing (NCT01755767)
Apatinib[49]	VEGFR2	Phase II (first line)	NR	NR	9.7 mo	4.2 mo	Favorable profile	Ongoing (NCT02329860)
Refametinib[50]	MEK	Phase II (+ sorafenib)	43%1	NR	290 d1	122 d1	High incidence of 3/4 grade adverse events	NR
Foretinib[51]	MET, RON, AXL, TIE-2, VEGFR	Phase I/II (first line)	79%	NR	NR	4.2 mo	Favorable profile	NR
Tepotinib[52]	c-MET	Phase Ib/II (vs sorafenib, first line) - Ongoing	NR	NR	NR	NR	Favorable profile	NR
Capmatinib[53]	c-MET	Phase I	NR	NR	NR	NR	Favorable profile	NR
Golvantinib[54]	c-MET	Phase I/IIb (+ sorafenib) - Ongoing	NR	NR	NR	NR	Favorable profile	NR
Emibetuzumab[55]	c-MET	Phase I (monotp vs emibetuzumab + erlotinib)	NR	NR	NR	NR	Favorable profile	NR
LY2157299[56]	TGF-β	Phase II (second-line)	NR	NR	36 wk2	12 wk2	Favorable profile	Ongoing
Pazopanib[57]	VEGFR1-3, PDGFRα-β, c-kit	Phase I	NR	NR	NR	NR	Favorable profile	NR
Axitinib[58]	VEGFR1-3	Phase II (vs placebo, second line)	NR	3.6 mo vs 1.9 mo; P = 0.004	12.7 mo vs 9.7 mo; P = 0.287	3.7 mo vs 1.9 mo; P = 0.006	Acceptable profile	NR

¹Best clinical response was observed in case of RAS mutations;

²Best clinical response was observed in case of AFP level decrease. DCR: Disease control rate; OS: Overall survival; TTP: Time-to-tumor progression; PFS: Progression free survival; NR: Not reported; NS: Not significant.