The US Food and Drug Administration (FDA) has expanded the indication for regorafenib (Stivarga, Bayer) to now include treatment for patients with hepatocellular carcinoma (HCC) who have previously been treated with the drug sorafenib (Nexavar, Bayer).
Expansion of regorafenib's indication marks the first FDA-approved treatment for a liver cancer in almost a decade.
"Limited treatment options are available for patients with liver cancer," said Richard Pazdur, MD, acting director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research and director of the FDA's Oncology Center of Excellence, in a statement.
"This is the first time patients with HCC have had an FDA-approved treatment that can be used if their cancer has stopped responding to initial treatment with sorafenib," said Dr Pazdur.
Regorafenib is an oral multikinase inhibitor that has shown antiangiogenic activity. It is already approved for the treatment of metastatic colorectal cancer and for use in the treatment of gastrointestinal stromal tumors that cannot be surgically removed and no longer respond to imatinib (Gleevec, Novartis) and sunitinib (Sutent, Pfizer).
Clinical Data in Liver Cancer
The expanded approval for use in liver cancer was based on the results of a phase 3 randomized trial that included 573 patients with progressive HCC who had previously undergone treatment with sorafenib.
Median overall survival was 10.6 months in the regorafenib group compared with 7.8 months in those receiving placebo, representing a significant reduction in the risk for death (hazard ratio [HR], 0.62; P < .001).
The median progression-free survival was also significantly longer in the regorafenib group vs placebo; at 3.1 months and 1.5 months, respectively (HR, 0.46; P < .001).
The disease control rate was significantly greater with regorafenib, at 65.2% vs 36.1% for placebo (P < .001); the complete or partial response rate was 10.6% for regorafenib compared with 4.1% for placebo (P = .01).
Adverse events of grade 3 or greater occurred in 79.7% of patients who received regorafenib and 58.5% of those in the placebo group. The most common grade 3 or greater adverse events were hypertension (15.2% vs 4.7%), hand-foot skin reactions (12.8% vs 0.5%), fatigue (9.1% vs 4.7%), and diarrhea (3.2% vs 0.0%).
This application for expanded use in liver cancer was granted priority review designation. This indication also received orphan drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.