CCR: Brivanib still shrouded in shadow under sorafenib

Recall introduced brivanib in advanced liver cancer Phase II clinical trials , the study brivanib as a first-line treatment of advanced liver cancer , and this study brivanib then as second-line therapy. Two multi-center clinical trials are , in fact, the same group of investigators who is the presiding officer of this study at UCLA Richard S. Finn.

The study included 46 who received anti-angiogenic treatment of advanced liver cancer patients , most of whom ( 93.5% ) discontinued because of tumor progression , a few because they can not tolerate the toxicity and withdrawal. Of which 43 received sorafenib ( the current standard treatment for advanced hepatocellular carcinoma ) , the other three had received thalidomide treatment. Acceptance of these first-line therapy , the median duration of 3.14 months. And as first-line therapy , the present study brivanib dose 800 mg / d orally.
Adverse reactions : 26 patients had Grade 3-5 adverse reactions, mainly grade 3-4 adverse events were hypertension, hyponatremia, thrombocytopenia and diarrhea. 4 adverse reactions occurred five patients , there has renal failure, cholecystitis , and disease progression. With sorafenib and Suni imatinib different , brivanib hand-foot syndrome caused by a lower proportion .
Efficacy assessment : This study used mRECIST criteria to assess tumor response to treatment , mRECIST is WHO RECIST criteria proposed by a small change made ​​by the AASLD-JNCI . RECIST traditional difference is , traditional RECIST simply to assess changes in tumor size , and ignores changes in the composition of the tumor . AASLD experts believe that as a rich blood supply of the tumor , liver blood supply in the healing process can also be used to reflect the changes in effect, therefore in mRECIST standard, the additional use of contrast-enhanced imaging methods to assess tumor blood supply (mRECIST standards more information, see Semin Liver Dis. 2010).

Overall, the effect is still exciting :
Partial remission two people ( response rate 4.3% ) , 19 stable disease , tumor control rate of the first two , and for 45.7% of tumor progression 19 people ;
The median survival was 9.79 months. Although the composition of the patients included in the study are different, but compared to sorafenib phase III clinical trial , the median survival time was 10.7 ( Europe and America ) and 6.5 months ( Asia Pacific ) , while brivanib as second-line therapy , the median survival time to obtain this quite good ; addition, the inclusion of this phase II clinical trial in patients with 2 / 3 from Asia, while Asian patients with advanced hepatocellular carcinoma prognosis seems even worse.
The median time to tumor progression was 2.7 months.
Serum alpha-fetoprotein (AFP) changes consistent with efficacy , AFP declined by more than half of the patients with a median survival time was 10.8 months, while the other patients , the median survival time was 7.3 months. Because animal studies can be used as brivanib collagen IV pharmacokinetics flag, so the researchers also measured plasma concentrations of this indicator . The authors found brivanib treatments significantly reduced the mean plasma concentration of type IV collagen . But do not know why the authors did not assess IV collagen concentration and efficacy relationship .
Overall, even as a second-line treatment , brivanib performance is quite satisfactory , but ultimately can not be out of the shadow of sorafenib , mainly have to look at it head to head with sorafenib phase III clinical trials.