Linifanib versus sorafenib in patients with advanced hepatocellular carcinoma: Results of a randomized phase III trial
Journal
Journal of Clinical Oncology
Journal Volume
33
Journal Issue
2
Pages
172-179
Date Issued
2015
Author(s)
Cainap C.
Qin S.
Huang W.-T.
Chung I.J.
Pan H.
Cheng Y.
Kudo M.
Kang Y.-K.
Toh H.-C.
Gorbunova V.
Eskens F.A.L.M.
Qian J.
McKee M.D.
Ricker J.L.
Carlson D.M.
El-Nowiem S.
Abstract
Purpose This open-label phase III trial evaluated efficacy and tolerability of linifanib versus sorafenib in patients with advanced hepatocellular carcinoma (HCC) without prior systemic therapy. Patients and Methods Patients were randomly assigned in a 1:1 ratio to linifanib 17.5 mg once daily or sorafenib 400 mg twice daily. Patients were stratified by region (Outside Asia, Japan, and rest of Asia), Eastern Cooperative Oncology Group performance score (ECOG PS; 0 or 1), vascular invasion or extrahepatic spread (yes or no), and hepatitis B virus (HBV) infection (yes or no). The primary end point of the study was overall survival (OS). Secondary end points were time to progression (TTP) and objective response rate (ORR) per RECIST v1.1. Results We randomly assigned 1,035 patients (median age, 60 years; Asian, 66.6%; ECOG PS 0, 65.2%; HBV, 49.1%; vascular invasion or extrahepatic spread, 70.1%). Median OS was 9.1 months on the linifanib arm (95% CI, 8.1 to 10.2) and 9.8 months on the sorafenib arm (95% CI, 8.3 to 11.0; hazard ratio [HR], 1.046; 95% CI, 0.896 to 1.221). For prespecified stratification subgroups, OS HRs ranged from 0.793 to 1.119 and the 95% CI contained 1.0. Median TTP was 5.4 months on the linifanib arm (95% CI, 4.2 to 5.6) and 4.0 months on the sorafenib arm (95% CI, 2.8 to 4.2; HR, 0.759; 95% CI, 0.643 to 0.895; P = .001). Best response rate was 13.0% on the linifanib arm versus 6.9% on the sorafenib arm. Grade 3/4 adverse events (AEs); serious AEs; and AEs leading to discontinuation, dose interruption, and reduction were more frequent with linifanib (all P <.001). Conclusion Linifanib and sorafenib had similar OS in advanced HCC. Predefined superiority and noninferiority OS boundaries were not met for linifanib and the study failed to meet the primary end point. TTP and ORR favored linifanib; safety results favored sorafenib. Copyright ? 2015 American Society of Clinical Oncology. ? 2014 by American Society of Clinical Oncology.
SDGs
Other Subjects
alanine aminotransferase; aspartate aminotransferase; bilirubin; linifanib; sorafenib; antineoplastic agent; carbanilamide derivative; indazole derivative; N-(4-(3-amino-1H-indazol-4-yl)phenyl)-N1-(2-fluoro-5-methylphenyl)urea; nicotinamide; protein kinase inhibitor; protein tyrosine kinase; sorafenib; abdominal pain; adult; advanced cancer; aged; alanine aminotransferase blood level; Article; ascites; Asia; aspartate aminotransferase blood level; asthenia; bilirubin blood level; cancer growth; cancer staging; chemotherapy induced anemia; controlled study; decreased appetite; diarrhea; drug dose reduction; drug efficacy; drug safety; drug tolerability; drug withdrawal; eastern cooperative oncology group performance score; epistaxis; fatigue; female; gingiva bleeding; hand foot syndrome; hepatic encephalopathy; hepatitis B; Hepatitis B virus; human; hyperbilirubinemia; hypertension; hypoglycemia; hypokalemia; hyponatremia; Japan; leukopenia; liver cell carcinoma; lymph vessel metastasis; major clinical study; male; neutropenia; open study; overall survival; phase 3 clinical trial; priority journal; randomized controlled trial; scoring system; side effect; thrombocyte count; thrombocytopenia; treatment duration; treatment response; very elderly; vomiting; analogs and derivatives; antagonists and inhibitors; Carcinoma, Hepatocellular; chemically induced; clinical trial; drug administration; Hand-Foot Syndrome; hypertension; Kaplan Meier method; Liver Neoplasms; middle aged; multicenter study; odds ratio; pathology; risk factor; treatment outcome; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Hepatocellular; Drug Administration Schedule; Female; Hand-Foot Syndrome; Humans; Hypertension; Indazoles; Kaplan-Meier Estimate; Liver Neoplasms; Male; Middle Aged; Niacinamide; Odds Ratio; Phenylurea Compounds; Protein Kinase Inhibitors; Receptor Protein-Tyrosine Kinases; Risk Factors; Treatment Outcome
Publisher
American Society of Clinical Oncology
Type
journal article