| General information |
| Database: | DB00916 |
| Objective: | Transarterial chemoembolization (TACE) is the current standard of treatment for unresectable intermediatestage hepatocellular carcinoma (hepatocellular carcinoma). 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. |
| Authors: | Kudo M, et al |
| Title: | Brivanib as adjuvant therapy to transarterial chemoembolization in patients with hepatocellular carcinoma: A randomizedphase III trial. |
| Journal: | Hepatology. |
| Year: | 2014 |
| PMID: | 24996197 |
| Trial Design |
| Clinical Trial Id: | NCT00908752 |
| Agent: | brivanib
|
| Target: | vascularendothelial growth factor and fibroblast growth factor receptors
|
| Cancer Type: | liver cancer |
| Cancer Subtype: | hepatocellular carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | multinational, randomized, doubleblind, placebocontrolled, phase III study |
| Key Patients Feature: | patients with TACEeligible hepatocellular carcinoma |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | brivanib versus placebo |
| Treatment Info: | pts were planned to be randomly assigned (1:1) after the first TACE to receive either brivanib 800 mg or placebo orally oncedaily. |
| Primary End Point: | overall survival (OS). |
| Secondary End Point: | 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 |
| Patients Number: | 870 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 48% in the brivanib group and 42% in the placebo group |
| Disease Control Rate: | 79% in both groups. |
| Median Time to Progression: | brivanib versus placebo: median TTP, 8.4 [95% CI: 6.710.2] vs. 4.9 [4.76.5] months; HR, 0.61 [0.480.77]; P < 0.0001 |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | 26.4 months (95% CI: 19.1 to not reached) in the brivanib group and 26.1 months (95% CI: 19.030.9) in the placebo group. |
| Adverse Event(agent arm): | Most frequent grade 34 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 |