| General information |
| Database: | DB00101 |
| Objective: | This multinational, randomized, doubleblind, phase III trial compared brivanib with sorafenib as firstline treatment for hepatocellular carcinoma. |
| Authors: | Johnson PJ, et al |
| Title: | Brivanib versus sorafenib as firstline therapy in patients with unresectable, advanced hepatocellular carcinoma: results from the randomizedphase III BRISKFL study. |
| Journal: | J Clin Oncol. |
| Year: | 2013 |
| PMID: | 23980084 |
| Trial Design |
| Clinical Trial Id: | NCT00858871. |
| Agent: | brivanib
|
| Target: | vascularendothelial growth factor and fibroblast growth factor receptors
|
| Cancer Type: | liver cancer |
| Cancer Subtype: | advanced hepatocellular carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a multinational, randomized, doubleblind, phase III trial |
| Key Patients Feature: | Advanced hepatocellular carcinoma patients who had no prior systemic therapy |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | sorafenib |
| Treatment Info: | pts 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: | Primary end point was OS. |
| Secondary End Point: | time to progression (TTP), objective response rate (ORR), disease control rate (DCR) based on modified mRECIST, and safety. |
| Patients Number: | 1150 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | ORR: 9% vs. 12% (95%CI: 0.99 to 2.13; Odds ratio 1.45 p=0.0569)(Sorafenib vs. Brivanib) |
| Disease Control Rate: | 65% vs. 66% (95%CI: 0.80 to 1.30; Odds ratio 1.45 p=0.8739)(Sorafenib vs. Brivanib) |
| Median Time to Progression: | 4.1(95%CI: 3.1 to 4.2) vs. 4.2 (95%CI:4.1 to 4.3) (Sorafenib vs. Brivanib) |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | Median OS was 9.9 months for sorafenib and 9.5 months for brivanib. |
| Adverse Event(agent arm): | 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%), handfootskin 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. |
| Conclusions: | Our study did not meet its primary end point of OS noninferiority for brivanib versus sorafenib. Hotheyver, both agents had similar antitumor activity, based on secondary efficacy end points. Brivanib had an acceptable safety profile, but was less welltolerated than sorafenib. |