FDA Approves Sorafenib for Patients With Inoperable Liver Cancer

Abstract

The U.S. Food and Drug Administration (FDA) on November 19 announced that it has approved sorafenib (Nexavar) for use in patients with hepatocellular carcinoma (HCC) when the cancer is inoperable. Sorafenib was originally approved in 2005 for the treatment of patients with advanced renal cell carcinoma. “In a randomized clinical trial, the group of patients with inoperable hepatocellular carcinoma who received sorafenib survived 2.8 months longer than the group of patients who didn’t receive the drug,” said Robert Justice, MD, director of the FDA’s division of drug oncology products. “This is an important new treatment option for patients who are fighting this very difficult form of cancer.” HCC accounts for 80%–90% of all liver cancers. This type of cancer can be difficult to surgically remove completely, thereby often making the disease fatal within 3–6 months. The American Cancer Society estimates that there will be 19,160 new cases and 16,780 deaths from cancer of the liver and intrahepatic bile duct in the United States in 2007. The FDA’s approval of sorafenib was based upon the results of an international randomized placebo-controlled trial in patients with inoperable HCC. The study was designed to compare the survival of a group of patients who received the drug with a group of similar patients who did not. A total of 602 patients were studied. Each patient received sorafenib or placebo. Both groups were comparable with regard to age, gender, race, cancer stage and other characteristics of their disease, and the types of cancer treatment they had received before entering the clinical trial. The trial was stopped after a planned interim analysis showed a statistically significant advantage in overall survival for patients who had received sorafenib. Patients who received sorafenib survived a median of 10.7 months whereas patients who received placebo survived a median of 7.9 months. A separate analysis showed that tumors progressed more slowly in patients who received sorafenib compared with patients who had received placebo. Sorafenib is a type of tyrosine kinase inhibitor. It interferes with molecules that are thought to be involved in chemical messages sent within cancer cells, in the formation of blood vessels that supply tumors, and in cell death. The most common adverse reactions that have been observed in patients taking sorafenib (for HCC or renal cell carcinoma) are fatigue, weight loss, rash or superficial skin shedding, hand or foot skin reaction, hair loss, diarrhea, anorexia, nausea, and abdominal pain. At least 20% of patients experienced ≥1 of these reactions. In patients with HCC, diarrhea was reported in 55% of patients who received sorafenib. Elevated serum lipase occurred in 40% of patients who received sorafenib, compared with 37% of patients who received placebo; and hypophosphatemia occurred in 35% of patients who received sorafenib compared with 11% of patients who received placebo. Sorafenib is manufactured by Bayer HealthCare AG, Leverkusen, Germany for Bayer Pharmaceuticals Corporation, West Haven, Connecticut, and by Onyx Pharmaceuticals, Inc, Emeryville, California.