Angiogenesis inhibition by the vascular endothelial growth factor receptor 
(VEGFR) and platelet-derived growth factor receptor (PDGFR) inhibitor sorafenib 
provides survival benefit in hepatocellular carcinoma (HCC); however, angiogenic 
escape from sorafenib may occur due to angiogenesis-associated fibroblast growth 
factor receptor (FGFR) pathway activation. In addition to VEGFR and PDGFR, 
dovitinib inhibits FGFR. Frontline oral dovitinib (500 mg/day, 5 days on, 2 days 
off; n = 82) versus sorafenib (400 mg twice daily; n = 83) was evaluated in an 
open-label, randomized phase 2 study of Asian-Pacific patients with advanced 
HCC. The primary and key secondary endpoints were overall survival (OS) and time 
to tumor progression (TTP) as determined by a local investigator, respectively. 
Patients included in the study were ineligible for surgical and/or locoregional 
therapies or had disease progression after receiving these therapies. The median 
OS (95% confidence interval [CI]) was 8.0 (6.6-9.1) months for dovitinib and 8.4 
(5.4-11.3) months for sorafenib. The median TTP (95% CI) per investigator 
assessment was 4.1 (2.8-4.2) months and 4.1 (2.8-4.3) months for dovitinib and 
sorafenib, respectively. Common any-cause adverse events included diarrhea 
(62%), decreased appetite (43%), nausea (41%), vomiting (41%), fatigue (35%), 
rash (34%), and pyrexia (30%) for dovitinib and palmar-plantar 
erythrodysesthesia syndrome (66%) and decreased appetite (31%) for sorafenib. 
Subgroup analysis revealed a significantly higher median OS for patients in the 
dovitinib arm who had baseline plasma soluble VEGFR1 (sVEGFR1) and hepatocyte 
growth factor (HGF) below median levels versus at or above the median levels 
(median OS [95% CI]: sVEGFR1, 11.2 [9.0-13.8] and 5.7 [4.3-7.0] months, 
respectively [P = .0002]; HGF, 11.2 [8.9-13.8] and 5.9 [5.0-7.6] months, 
respectively [P = 0.0002]).
CONCLUSION: Dovitinib was well tolerated, but activity was not greater than 
sorafenib as a frontline systemic therapy for HCC. Based on these data, no 
subsequent phase 3 study has been planned. (Hepatology 2016;64:774-784).