Linifanib Fails to Improve Survival in Hepatocellular Cancer

David H. Ilson, MD, PhD reviewing Cainap C et al. J Clin Oncol 2015 Jan 10.

Overall survival was similar with linifanib versus sorafenib.

Sorafenib, a multitargeted tyrosine kinase inhibitor, is the standard therapy for advanced hepatocellular cancer, but it has only a modest impact on survival.

Investigators now report results of an industry-sponsored, international, multicenter, randomized, open-label, phase III trial that compares sorafenib with linifanib, a new multitargeted tyrosine kinase inhibitor, in 1035 patients (median age, 60 years) with unresectable or metastatic hepatocellular cancer. Most patients were male (85%) and Asian (67%) and had hepatitis B virus infection (53%), Child-Pugh Class A liver function (94%), and performance status 0 (64%).

Overall survival (the primary endpoint) was not improved with linifanib versus sorafenib (9.1 and 9.8 months, respectively). Linifanib recipients experienced significantly improved time to progression (5.4 vs. 4.0 months), progression-free survival (4.2 vs. 2.9 months), and objective response rate (13.0% vs. 6.9%). Linifanib recipients also experienced significantly higher rates of grade 3 and 4 adverse events (85% vs. 75%), including more hypertension, fatigue, hepatic encephalopathy, ascites, and thrombocytopenia. Survival analyses failed to indicate either superiority or noninferiority for linifanib.

Citation(s):

Cainap C et al. Linifanib versus sorafenib in patients with advanced hepatocellular carcinoma: Results of a randomized phase III trial. J Clin Oncol 2015 Jan 10; 33:172.