e15632 Background:Conventional chemotherapy has limited role in metastatic unresectable hepatocellular carcinoma (HCC). Sorafenib is currently approved for metastatic unresectable HCC. We wanted to assess the efficacy and safety of other tyrosine kinase inhibitors (TKI) targeting vascular endothelial growth factor (VEGF) receptor such as brivanib, linifanib and regorafenib in metastatic HCC. Methods: We have searched electronic databases Pubmed, Google scholar to identify published trials using brivanib, linifanib and regorafenib in HCC. The outcomes evaluated were overall survival, time to disease progression (TTDP) and adverse effects. Hazard ratios (HR) with their respective 95% confidence intervals (CI) were then computed using the appropriate model for categorical variables. We used STATA 13.0 and Comprehensive Meta Analysis 2.0 software for all analyses. Results: We included seven randomized control studies. A combined analysis of these seven randomised control trials showed improved overall survival (OS) in VEGF-TKI group when compared to placebo HR - 0.79; (95% CI 0.62-1.00). However, there was no significant survival benefit of the newer VEGF receptor inhibitors when compared to sorafenib (HR - 1.05; 95% CI 0.95-1.17). The time to disease progression (TTDP) was significantly better in VEGF-TKI group as compared to placebo (HR - 0.61; 95% CI 0.39-0.97). However, there was no significant difference in TTDP between VEGF-TKI group and Sorafenib (HR - 0.88; 95% CI 0.66-1.16). Adverse effects were noted to be higher in VEGF-TKI group when compared to placebo (HR- 1.07; 95% CI 1.01-1.13). Conclusions: Treatment with TKI targeting VEGF receptor is associated with a significant improvement in OS and TTDP with tolerable side effect profile. Inhibiting the VEGF receptor pathway could lead to improved outcomes in HCC.
Relative dose intensity over the first four weeks of lenvatinib therapy is a factor of favorable response and overall survival in patients with unresectable hepatocellular carcinoma
