Randomized, open-label phase 2 study comparing frontline dovitinib versus sorafenib in patients with advanced hepatocellular carcinoma.

ABSTRACT

UNLABELLED 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;64774-784).