Brivanib as adjuvant therapy to transarterial chemoembolization in patients with hepatocellular carcinoma: A randomized phase III trial
© 2014 by the American Association for the Study of Liver Diseases. Transarterial chemoembolization (TACE) is the current standard of treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC). Brivanib, a selective dual inhibitor of vascular endothelial growth factor and fibroblas...
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th-mahidol.348752018-11-09T10:06:33Z Brivanib as adjuvant therapy to transarterial chemoembolization in patients with hepatocellular carcinoma: A randomized phase III trial Masatoshi Kudo Guohong Han Richard S. Finn Ronnie T.P. Poon Jean Frederic Blanc Lunan Yan Jijin Yang Ligong Lu Won Young Tak Xiaoping Yu Joon Hyeok Lee Shi Ming Lin Changping Wu Tawesak Tanwandee Guoliang Shao Ian B. Walters Christine Dela Cruz Valerie Poulart Jian Hua Wang Kindai University School of Medicine The Fourth Military Medical University David Geffen School of Medicine at UCLA The University of Hong Kong CHU Hopitaux de Bordeaux West China Hospital of Sichuan University Changhai Hospital Guangdong General Hospital Kyungpook National University Hospital Hunan Provincial Tumor Hospital SungKyunKwan University, School of Medicine Chang Gung Memorial Hospital First People's Hospital of Changzhou Mahidol University Zhejiang Cancer Hospital Bristol-Myers Squibb Bristol-Myers Squibb Zhongshan Hospital Shanghai Medicine © 2014 by the American Association for the Study of Liver Diseases. Transarterial chemoembolization (TACE) is the current standard of treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC). Brivanib, a selective dual inhibitor of vascular endothelial growth factor and fibroblast growth factor signaling, may improve the effectiveness of TACE when given as an adjuvant to TACE. In this multinational, randomized, double-blind, placebo-controlled, phase III study, 870 patients with TACE-eligible HCC were planned to be randomly assigned (1:1) after the first TACE to receive either brivanib 800 mg or placebo orally once-daily. The primary endpoint was overall survival (OS). Secondary endpoints included time to disease progression (TTDP; a composite endpoint based on development of extrahepatic spread or vascular invasion, deterioration of liver function or performance status, or death), time to extrahepatic spread or vascular invasion (TTES/VI), rate of TACE, and safety. Time to radiographic progression (TTP) and objective response rate were exploratory endpoints. The trial was terminated after randomization of 502 patients (brivanib, 249; placebo, 253) when two other phase III studies of brivanib in advanced HCC patients failed to meet OS objectives. At termination, median follow-up was approximately 16 months. Intention-to-treat analysis showed no improvement in OS with brivanib versus placebo (median, 26.4 [95% confidence interval {CI}: 19.1 to not reached] vs. 26.1 months [19.0-30.9]; hazard ratio [HR]: 0.90 [95% CI: 0.66-1.23]; log-rank P=0.5280). Brivanib improved TTES/VI (HR, 0.64 [95% CI: 0.45-0.90]), TTP (0.61 [0.48-0.77]), and rate of TACE (0.72 [0.61-0.86]), but not TTDP (0.94 [0.72-1.22]) versus placebo. Most frequent grade 3-4 adverse events included hyponatremia (brivanib, 18% vs. placebo, 5%) and hypertension (13% vs. 3%). Conclusions: In this study, brivanib as adjuvant therapy to TACE did not improve OS. (Hepatology 2014;60:1697-1707). 2018-11-09T03:06:33Z 2018-11-09T03:06:33Z 2014-01-01 Article Hepatology. Vol.60, No.5 (2014), 1697-1707 10.1002/hep.27290 15273350 02709139 2-s2.0-84922252607 https://repository.li.mahidol.ac.th/handle/123456789/34875 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84922252607&origin=inward |
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Medicine Masatoshi Kudo Guohong Han Richard S. Finn Ronnie T.P. Poon Jean Frederic Blanc Lunan Yan Jijin Yang Ligong Lu Won Young Tak Xiaoping Yu Joon Hyeok Lee Shi Ming Lin Changping Wu Tawesak Tanwandee Guoliang Shao Ian B. Walters Christine Dela Cruz Valerie Poulart Jian Hua Wang Brivanib as adjuvant therapy to transarterial chemoembolization in patients with hepatocellular carcinoma: A randomized phase III trial |
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© 2014 by the American Association for the Study of Liver Diseases. Transarterial chemoembolization (TACE) is the current standard of treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC). Brivanib, a selective dual inhibitor of vascular endothelial growth factor and fibroblast growth factor signaling, may improve the effectiveness of TACE when given as an adjuvant to TACE. In this multinational, randomized, double-blind, placebo-controlled, phase III study, 870 patients with TACE-eligible HCC were planned to be randomly assigned (1:1) after the first TACE to receive either brivanib 800 mg or placebo orally once-daily. The primary endpoint was overall survival (OS). Secondary endpoints included time to disease progression (TTDP; a composite endpoint based on development of extrahepatic spread or vascular invasion, deterioration of liver function or performance status, or death), time to extrahepatic spread or vascular invasion (TTES/VI), rate of TACE, and safety. Time to radiographic progression (TTP) and objective response rate were exploratory endpoints. The trial was terminated after randomization of 502 patients (brivanib, 249; placebo, 253) when two other phase III studies of brivanib in advanced HCC patients failed to meet OS objectives. At termination, median follow-up was approximately 16 months. Intention-to-treat analysis showed no improvement in OS with brivanib versus placebo (median, 26.4 [95% confidence interval {CI}: 19.1 to not reached] vs. 26.1 months [19.0-30.9]; hazard ratio [HR]: 0.90 [95% CI: 0.66-1.23]; log-rank P=0.5280). Brivanib improved TTES/VI (HR, 0.64 [95% CI: 0.45-0.90]), TTP (0.61 [0.48-0.77]), and rate of TACE (0.72 [0.61-0.86]), but not TTDP (0.94 [0.72-1.22]) versus placebo. Most frequent grade 3-4 adverse events included hyponatremia (brivanib, 18% vs. placebo, 5%) and hypertension (13% vs. 3%). Conclusions: In this study, brivanib as adjuvant therapy to TACE did not improve OS. (Hepatology 2014;60:1697-1707). |
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Kindai University School of Medicine |
author_facet |
Kindai University School of Medicine Masatoshi Kudo Guohong Han Richard S. Finn Ronnie T.P. Poon Jean Frederic Blanc Lunan Yan Jijin Yang Ligong Lu Won Young Tak Xiaoping Yu Joon Hyeok Lee Shi Ming Lin Changping Wu Tawesak Tanwandee Guoliang Shao Ian B. Walters Christine Dela Cruz Valerie Poulart Jian Hua Wang |
format |
Article |
author |
Masatoshi Kudo Guohong Han Richard S. Finn Ronnie T.P. Poon Jean Frederic Blanc Lunan Yan Jijin Yang Ligong Lu Won Young Tak Xiaoping Yu Joon Hyeok Lee Shi Ming Lin Changping Wu Tawesak Tanwandee Guoliang Shao Ian B. Walters Christine Dela Cruz Valerie Poulart Jian Hua Wang |
author_sort |
Masatoshi Kudo |
title |
Brivanib as adjuvant therapy to transarterial chemoembolization in patients with hepatocellular carcinoma: A randomized phase III trial |
title_short |
Brivanib as adjuvant therapy to transarterial chemoembolization in patients with hepatocellular carcinoma: A randomized phase III trial |
title_full |
Brivanib as adjuvant therapy to transarterial chemoembolization in patients with hepatocellular carcinoma: A randomized phase III trial |
title_fullStr |
Brivanib as adjuvant therapy to transarterial chemoembolization in patients with hepatocellular carcinoma: A randomized phase III trial |
title_full_unstemmed |
Brivanib as adjuvant therapy to transarterial chemoembolization in patients with hepatocellular carcinoma: A randomized phase III trial |
title_sort |
brivanib as adjuvant therapy to transarterial chemoembolization in patients with hepatocellular carcinoma: a randomized phase iii trial |
publishDate |
2018 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/34875 |
_version_ |
1763491565787938816 |