| General information |
| Database: | DB00104 |
| Objective: | An unmet medical need persists for patients with hepatocellular carcinoma whose tumors do not respond to sorafenib or who cannot tolerate it. This study assessed brivanib in patients with hepatocellular carcinoma who had been treated with sorafenib. |
| Authors: | Llovet JM, et al |
| Title: | Brivanib in patients with advanced hepatocellular carcinoma who were intolerant to sorafenib or for whom sorafenib failed: results from the randomizedphase III BRISKPS study. |
| Journal: | J Clin Oncol. |
| Year: | 2013 |
| PMID: | 23980090 |
| Trial Design |
| Clinical Trial Id: | NCT00825955. |
| 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 multicenter, doubleblind, randomized, placebocontrolledphase III trial |
| Key Patients Feature: | patients with advanced hepatocellular carcinoma who progressed on/after or were intolerant to sorafenib |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | placebo plus best supportive care |
| Treatment Info: | patients were randomly assigned (2:1) to receive brivanib 800 mg orally once per day plus best supportive care (BSC) or placebo plus BSC. |
| Primary End Point: | OS. |
| Secondary End Point: | TTP, ORR, and disease control rate based on mRECIST and safety. |
| Patients Number: | 395 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | ORR of 10% vs 2% for placebo (OR, 5.72). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | a median TTP of 4.2 vs 2.7 (HR, 0.56; 95% CI, 0.42 to 0.76; P < .001), |
| Median OS A vs. C: | 9.4 vs 8.2, HR 0.89; 95.8% CI, 0.69 to 1.15; P = .3307 |
| Adverse Event(agent arm): | Study discontinuation due to treatmentrelated adverse events (AEs) occurred in 61 brivanib patients (23%) and nine placebo patients (7%). The most frequent treatmentrelated grade 3 to 4 AEs for brivanib included hypertension (17%), fatigue (13%), hyponatremia (11%), and decreased appetite (10%). |
| Conclusions: | In patients with hepatocellular carcinoma who had been treated with sorafenib, brivanib did not significantly improve OS. The observed benefit in the secondary outcomes of TTP and ORR warrants further investigation. |