| General information |
| Database: | DB00894 |
| Objective: | Brivanib, a selective dual inhibitor of fibroblast growth factor and VEGF signaling, has demonstrated encouraging antitumor activity in preclinical andphase I studies. they performed a phase II openlabel study of brivanib as firstline therapy in patients with unresectable, locally advanced, or metastatic hepatocellular carcinoma. |
| Authors: | Park JW, et al |
| Title: | Phase II, openlabel study of brivanib as firstline therapy in patients with advanced hepatocellular carcinoma. |
| Journal: | Clin Cancer Res. |
| Year: | 2011 |
| PMID: | 21349999 |
| Trial Design |
| Clinical Trial Id: | NCT00355238 |
| 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: | Phase II, openlabel study |
| Key Patients Feature: | patients with unresectable, locally advanced, or metastatic hepatocellular carcinoma. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Brivanib was administered orally at a dose of 800 mg once daily |
| Primary End Point: | 6month progression free survival, progression free survival rate |
| Secondary End Point: | tumor response rate, time to response, duration of response, median progression free survival, median overall survival, disease control rate (complete response, partial response, or stable disease more than and equal to 42 days), and safety and tolerability. |
| Patients Number: | 55 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | 51% |
| Median Time to Progression: | IRRC time to progression was 2.8 months (95% CI, 1.4-3.5) and investigator time to progression was 2.7 months (95% CI, 1.5-2.8). |
| Median PFS A vs. C: | 2.7 months (1.43.0). |
| Median OS A vs. C: | 10 (6.815.2) months |
| Adverse Event(agent arm): | hirteen patients experienced drugrelated serious AEs, which were grade 3/4 in 10 patients (Table 4). Twentysix percent of patients had a diastolic blood pressure greater than 100mm Hg and only 1.8% of patients had a diastolic blood pressure greater than 110mm Hg during the treatment course. In addition, 25 patients (46%) had anygrade hypertension as a reported AE; grade 3/4 in 6 patients (11%). Grade 2 hypertension led to treatment discontinuation in 1 patient. Six patients (11%) experienced minor (grade 1/2, except for one grade 3 esophageal varices hemorrhage; none requiring blood transfusion) gastrointestinal bleeding events, including 2 minor anal bleedings (online Supplementary section Table A2). Of note, only 2 patients (4%) experienced handfoot syndrome, which was grade 1/2 in 1 patient and grade 3 in 1 patient, which were considered drug related. Three patients (5.5%) had grade 3 encephalopathy, which was considered drugrelated in 1 patient. Of the 35 deaths that occurred (1 within 30 days of starting the trial and 6 within 30 days of the last dose), none were considered treatment related (30 patients died due to disease progression, 5 died due to other reasons). Eight patients (14.5%) had grade 3/4 hyponatremia; however, some patients may have entered the study with up to grade 3 hyponatremia; see online supplementary section D). |
| Conclusions: | Brivanib as firstline therapy demonstrates promising antitumor activity and a manageable safety profile in patients with advanced, unresectable hepatocellular carcinoma. |