Sorafenib (Nexavar) Fails Phase III Trial in Patients With Liver Cancer
Treatment has no effect on recurrence-free survival
A phase III study evaluating the investigational use of sorafenib (Nexavar, Bayer HealthCare/Onyx Pharmaceuticals) as an adjuvant treatment for patients with hepatocellular carcinoma (HCC) who had no detectable disease after surgical resection or local ablation, did not meet its primary endpoint of improving recurrence-free survival.
The randomized, double-blind, placebo-controlled STORM (Sorafenib as Adjuvant Treatment in the Prevention Of Recurrence of Hepatocellular CarcinoMa) trial was an international study that evaluated the clinical benefit of sorafenib versus placebo as an adjuvant treatment in patients with HCC following potential curative treatment (i.e., surgical resection or local ablation). The trial included approximately 1,100 patients, who were randomly assigned to receive either 400 mg of sorafenib twice daily or matching placebo for 4 years or until disease recurrence, whichever occurred first.
The study’s primary endpoint was recurrence-free survival. Secondary endpoints included the time to recurrence of HCC (intrahepatic and extrahepatic) and overall survival. Safety and tolerability were also assessed.
Hepatocellular carcinoma is the most common form of liver cancer and is responsible for approximately 80% of the primary malignant liver tumors in adults. Liver cancer is the sixth most common cancer in the world and is the second most common cause of death from cancer worldwide. More than 780,000 cases of liver cancer are diagnosed worldwide each year (more than 30,000 in the U.S.), and the incidence is increasing. In 2012, approximately 746,000 people died of liver cancer worldwide, including about 24,000 in the U.S.
Nexavar (sorafenib) is approved in the U.S. for patients with unresectable hepatocellular carcinoma, for patients with advanced renal cell carcinoma, and for patients with locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine treatment.
Sorafenib is thought to inhibit both the tumor cell and tumor vasculature. In in vitro studies, the drug has been shown to inhibit multiple kinases thought to be involved in both cell proliferation and angiogenesis — two important processes that enable cancer growth. These kinases include Raf kinase; vascular endothelial growth factor receptor (VEGFR)-1, -2, and -3; platelet-derived growth factor receptor (PDGFR)-B; FMS-like tyrosine kinase (FLT)-3; and rearranged during transfection (RET) transmembrane tyrosine kinase.
Source: PR Newswire; March 11, 2014.