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Abstract Details
Randomized, Open-Label Phase 2 Study Comparing Frontline Dovitinib vs Sorafenib in Patients With Advanced Hepatocellular Carcinoma
Cheng AL1, Thongprasert S2, Lim HY3, Sukeepaisarnjaroen W4, Yang TS5, Wu CC6, Chao Y7, Chan SL8, Kudo M9, Ikeda M10, Kang YK11, Pan H12, Numata K13, Han G14, Balsara B15, Zhang Y15, Rodriguez AM16, Zhang Y15, Wang Y15, Poon RT17. Hepatology. 2016 Apr 15. doi: 10.1002/hep.28600. [Epub ahead of print]
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Abstract
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) vs sorafenib (400 mg, twice daily; n = 83) was evaluated in an open-label, randomized phase 2 study of Asian-Pacific patients with advanced HCC. Primary and key secondary endpoints were overall survival (OS) and time to tumor progression (TTP) per local investigator, respectively. Eligible patients had progressed after or were ineligible for surgical and/or locoregional therapies. Median OS (95% CI) was 8.0 (6.6-9.1) months for dovitinib and 8.4 (5.4-11.3) months for sorafenib. Median TTP (95% CI) per investigator assessment was 4.1 (2.8-4.2) 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 showed higher median OS for patients on dovitinib, with baseline plasma soluble VEGFR1 (sVEGFR1) and hepatocyte growth factor (HGF) < median levels relative to ≥ 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 frontline systemic therapy for HCC. Based on these data, no subsequent phase 3 study is planned.