https://scholars.lib.ntu.edu.tw/handle/123456789/487300
標題: | Brivanib versus sorafenib as first-line therapy in patients with unresectable, advanced hepatocellular carcinoma: Results from the randomized phase III BRISK-FL study | 作者: | Johnson P.J. Qin S. Park J.-W. Poon R.T.P. Raoul J.-L. Philip P.A. CHIH-HUNG HSU Hu T.-H. Heo J. Xu J. Lu L. Chao Y. Boucher E. Han K.-H. Paik S.-W. Robles-Aviña J. Kudo M. Yan L. Sobhonslidsuk A. Komov D. Decaens T. Tak W.-Y. Jeng L.-B. Liu D. Ezzeddine R. Walters I. ANN-LII CHENG |
公開日期: | 2013 | 出版社: | American Society of Clinical Oncology | 卷: | 31 | 期: | 28 | 起(迄)頁: | 3517-3524 | 來源出版物: | Journal of Clinical Oncology | 摘要: | Purpose: Brivanib is a dual inhibitor of vascular-endothelial growth factor and fibroblast growth factor receptors that are implicated in the pathogenesis of hepatocellular carcinoma (HCC). Our multinational, randomized, double-blind, phase III trial compared brivanib with sorafenib as first-line treatment for HCC. Patients and Methods: Advanced HCC patients who had no prior systemic therapy were randomly assigned (ratio, 1:1) to receive sorafenib 400 mg twice daily orally (n = 578) or brivanib 800 mg once daily orally (n = 577). Primary end point was overall survival (OS). Secondary end points included time to progression (TTP), objective response rate (ORR), disease control rate (DCR) based on modified Response Evaluation Criteria in Solid Tumors (mRECIST), and safety. Results: The primary end point of OS noninferiority for brivanib versus sorafenib in the per-protocol population (n = 1,150) was not met (hazard ratio [HR], 1.06; 95.8% CI, 0.93 to 1.22), based on the prespecified margin (upper CI limit for HR ? 1.08). Median OS was 9.9 months for sorafenib and 9.5 months for brivanib. TTP, ORR, and DCR were similar between the study arms. Most frequent grade 3/4 adverse events for sorafenib and brivanib were hyponatremia (9% and 23%, respectively), AST elevation (17% and 14%), fatigue (7% and 15%), hand-footskin reaction (15% and 2%), and hypertension (5% and 13%). Discontinuation as a result of adverse events was 33% for sorafenib and 43% for brivanib; rates for dose reduction were 50% and 49%, respectively. Conclusion: Our study did not meet its primary end point of OS noninferiority for brivanib versus sorafenib. However, both agents had similar antitumor activity, based on secondary efficacy end points. Brivanib had an acceptable safety profile, but was less well-tolerated than sorafenib. Copyright ? 2017 American Society of Clinical Oncology. All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84890274647&doi=10.1200%2fJCO.2012.48.4410&partnerID=40&md5=5836f57dd54c1a3dd1a48c8882b8ba0b https://scholars.lib.ntu.edu.tw/handle/123456789/487300 |
ISSN: | 0732-183X | DOI: | 10.1200/JCO.2012.48.4410 | SDG/關鍵字: | alanine aminotransferase; alpha fetoprotein; aspartate aminotransferase; brivanib; sorafenib; alanine; brivanib; carbanilamide derivative; nicotinamide; protein kinase inhibitor; sorafenib; triazine derivative; abdominal pain; adult; adverse outcome; alanine aminotransferase blood level; alcohol consumption; alopecia; antineoplastic activity; Article; aspartate aminotransferase blood level; constipation; controlled study; decreased appetite; diarrhea; dizziness; double blind procedure; drug efficacy; drug safety; drug tolerance; drug withdrawal; dysphonia; fatigue; female; fever; hand foot syndrome; headache; hepatitis B; hepatitis C; human; hyperbilirubinemia; hypertension; hyponatremia; liver cell carcinoma; major clinical study; male; nausea; overall survival; phase 3 clinical trial; priority journal; quality of life; randomized controlled trial; rash; side effect; skin manifestation; treatment duration; vomiting; aged; analogs and derivatives; cancer staging; Carcinoma, Hepatocellular; clinical trial; comparative study; follow up; Liver Neoplasms; middle aged; mortality; multicenter study; pathology; prognosis; survival rate; very elderly; young adult; Adult; Aged; Aged, 80 and over; Alanine; Carcinoma, Hepatocellular; Double-Blind Method; Female; Follow-Up Studies; Humans; Liver Neoplasms; Male; Middle Aged; Neoplasm Staging; Niacinamide; Phenylurea Compounds; Prognosis; Protein Kinase Inhibitors; Survival Rate; Triazines; Young Adult |
顯示於: | 腫瘤醫學研究所 |
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