BETHESDA, MD 28 September 2012—
FDA and Bayer Healthcare and Onyx Pharmaceuticals (PDF) on September 27 announced the approval of regorafenib oral tablets for the treatment of metastatic colorectal cancer.
Regorafenib, a kinase inhibitor, is marketed as Stivarga. The drug is indicated for use in patients previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, antivascular endothelial growth factor therapy, and, for patients with a wild-type Kras gene, antiepidermal growth factor receptor therapy.
FDA-approved labeling (PDF) for regorafenib describes the drug as a small molecule inhibitor of multiple kinases involved in normal cellular functions as well as oncogenesis, tumor angiogenesis, and maintenance of the tumor microenvironment.
In the clinical trial that led to the drug's approval, regorafenib treatment plus best supportive care increased patients' overall survival by 1.4 months—roughly 42 days—and progression-free survival by 0.3 month—roughly 9 days—compared to best supportive care plus a placebo.
The recommended dosage of regorafenib is four 40-mg tablets taken with a low-fat breakfast, which is defined as a meal containing less than 30% fat. Patients should take the drug once daily for the first 21 days of each 28-day treatment cycle. Treatment cycles should continue until disease progression or unacceptable toxicity occurs.
Dosage interruptions, reductions, and discontinuations are recommended if certain adverse events occur. These include hand–foot skin reactions, symptomatic hypertension, liver-enzyme abnormalities, and serious adverse events. Specific dosage recommendations for these situations are provided in the labeling.
A boxed warning in the labeling for regorafenib instructs clinicians to monitor patients' liver function during treatment with the drug, which was associated with severe and fatal liver toxicity in clinical trials.
The most common adverse events reported by clinical trial participants treated with regorafenib included fatigue, loss of appetite, hand–foot skin reactions, diarrhea, mucositis, infection, hypertension, and voice disorders. Rare but serious cases of liver toxicity, hemorrhage, and gastrointestinal perforation were also reported.
Regorafenib is available in 28-tablet bottles, with three bottles per package. The tablets should be stored at controlled room temperature in the original bottles, which contain a desiccant. Any tablets not used within 28 days of opening a bottle should be discarded.