Predictive biomarkers of sorafenib efficacy in advanced hepatocellular carcinoma: Are we getting there?

Table 2 Studies on predictive and prognostic markers for advanced hepatocellular carcinoma -- tissue biomarkers, clinical parameters, and others

Markers	Authors	Treatment	Findings supportive of
			Predictive markers	Prognostic markers	Others
Tissue biomarkers
p-ERK expression	Abou-Alfa et al[57]	Sorafenib	High p-ERK → longer TTP	-	-
	Ozenne et al[58]	Sorafenib	No predictive values	-	-
	Chen et al[59]	Sorafenib	High p-ERK → longer TTP	-	-
p-c-Jun expression	Hagiwara et al[61]	Sorafenib	High p-c-Jun expression → poor response, shorter TTP	p-c-Jun expression → shorter OS	-
Clinical parameter
DCE-MRI	Hsu et al[63]	Sorafenib plus UFT	High baseline Ktrans or decreased Ktrans after treatment→ higher DCR	Vascular response1→ longer OS	Vascular response1→ longer PFS
Positron emission tomography	Lee et al[68]	Sorafenib	-	Low SUV → longer OS	Low SUV → longer PFS
Hypertension	Estfan et al[71]	Sorafenib	Hypertension → longer TTP (?)2	Hypertension → longer OS	-
	Otsuka et al[72]	Sorafenib	No predictive values	No prognostic values	-
Skin toxicity	Otsuka et al[72]	Sorafenib	No predictive values	Skin toxicities → longer OS	-
	Lee et al[73]	Sorafenib	-	≥ grade 2 skin toxicities → longer OS	≥ grade 2 skin toxicities → longer PFS
	Vincenzi et al[74]	Sorafenib	Early4≥ grade 1 skin toxicities → longer DCR and TTP	Early ≥ grade 1 skin toxicities → longer OS3	-
Hepatitis etiology	Shao et al[78]	Sorafenib vs other treatments	Synthesized hazard ratio for overall mortality: 0.65 in patients with HCV etiology and 0.87 in patients with non-HCV etiology
Novel approaches
FGF3/FGF4 amplification	Arao et al[79]	Sorafenib	FGF3/FGF4 amplification → higher tumor response	-	-
VEGFA amplification	Horwitz et al[85]	Sorafenib	-	VEGFA amplification → longer OS	-
p-Mapk14, p-Atf2 expression	Rudalska et al[86]	Sorafenib	-	High p-Mapk14 or p-Atf2 expression → shorter OS	-

¹Defined as ≥ 40% decreased in K^trans after treatment;

²Statistical values of the comparison not reported;

³Borderline statistical significance;

⁴Within the first month of treatment. DCE-MRI: Dynamic contrast-enhanced magnetic resonance imaging; DCR: Disease control rate; OS: Overall survival; p-: Phospho-; PBMC: Peripheral blood mononuclear cells; PFS: Progression-free survival; TTP: Time to progression; UFT: Tegafur/uracil.