Nexavar becomes first drug approved for liver cancer

November 19, 2007

The Food and Drug Administration added liver cancer to the approved indications of Nexavar (sorafenib), an oral targeted therapy initially approved for kidney cancer. The approval made Nexavar the first systemic drug therapy for unresectable hepatocellular carcinoma (HCC),  and the only drug therapy shown to significantly improve overall survival in patients with the disease.

HCC, the most common form of liver cancer, is responsible for about 90 percent of the primary malignant liver tumors in adults. Liver cancer is the sixth most common cancer in the world and the third leading cause of cancer-related deaths globally. More than 600,000 cases of liver cancer are diagnosed worldwide each year (about 19,000 in the United States) and incidence is increasing.

“The American Liver Foundation (ALF) is always pleased when new therapies prove effective for those affected by liver disease. Researchers worldwide, including those supported by ALF, have spent decades studying liver cancer,” said James L. Boyer, MD, chairman, board of directors, American Liver Foundation. “This new treatment provides a valuable option for liver cancer patients and will enable ALF to further promote the treatment of liver disease through our education and advocacy efforts.”

The FDA approval was based on positive data from the international, phase 3, placebo-controlled Sorafenib HCC Assessment Randomized Protocol (SHARP) trial which demonstrated that Nexavar improved overall survival by 44 percent in patients with HCC versus placebo. Median overall survival was 10.7 months in Nexavar-treated patients compared to 7.9 months in those taking placebo. No indication of imbalances was observed in serious adverse event rates between the Nexavar and placebo-treated groups with the most commonly observed adverse events in patients receiving Nexavar being diarrhea and hand-foot skin reaction.

Nexavar targets both the tumor cell and tumor vasculature. In preclinical studies, Nexavar has been shown to target members of two classes of kinases known to be involved in both cell proliferation (growth) and angiogenesis (blood supply) – two important processes that enable cancer growth. These kinases included Raf kinase, VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-B, KIT, FLT-3, and RET. Preclinical models have also demonstrated that Raf/MEK/ERK has a role in HCC. Therefore, blocking signaling through Raf-1 may offer therapeutic benefits in HCC.

In 2005, Nexavar became the first new treatment in more than a decade for advanced kidney cancer and is currently approved in more than 60 countries for this indication. Nexavar is also being evaluated as a single agent or combination treatment in a wide range of other cancers, including adjuvant therapy for kidney cancers, breast cancer, non-small cell lung cancer (NSCLC), and metastatic melanoma.