The FDA has given priority review designation to sorafenib (Nexavar) for the treatment of locally advanced or metastatic radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC). If approved, sorafenib would be the first new drug to become available for the treatment of this aggressive form of thyroid cancer in more than 40 years.
According to a statement from the two manufacturers of the drug, Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals, the scheduled date for completion of review by the FDA of the supplemental New Drug Application is December 25, 2013.
“We are very pleased that the FDA has chosen to grant Priority Review to sorafenib,” said Pamela A. Cyrus, MD, vice president and head of US Medical Affairs for Bayer HealthCare Pharmaceuticals, in a statement. “This is an important milestone for sorafenib, and the designation highlights the urgent need for new treatments for patients with this type of thyroid cancer who have limited or no treatment options.”
Of the more than 60,000 cases of thyroid cancer diagnosed annually in the United States, DTC accounts for about 85% of those cases, making it the most common subtype of the disease. The cure rates for DTC are generally high when patients are treated with surgery or RAI. However, between 5% and 15% of patients develop RAI resistance, and these patients typically have an expected survival of 2.5 to 3.5 years. No standard therapy exists for patients who experience disease progression.
Sorafenib, a tyrosine kinase inhibitor, inhibits multiple kinases, including the Raf kinase, VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-B, KIT, FLT-3 and RET, which are associated with tumor cell proliferation and angiogenesis. The drug is currently approved by the FDA to treat unresectable hepatocellular carcinoma and advanced renal cell carcinoma.
The priority review was granted on the basis of the results of the DECISION study, which were first presented at the 49th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois, in June.
Results were available for 417 patients with metastatic, RAI-resistant DTC whose disease had progressed in the past 14 months. Those patients were randomized to receive either 400 mg of sorafenib twice daily (n = 207) or a placebo (n = 210). Patients whose disease progressed on the control arm were allowed to cross over to the sorafenib arm. The researchers reported that approximately 70% of patients in the placebo arm crossed over during the course of the study. The primary endpoint of the study was progression-free survival (PFS). The study found that the median PFS in patients who received sorafenib was 10.8 months compared with 5.8 months in the placebo arm (hazard ratio [HR] 0.58; 95% CI, 0.45-0.75; P
<.0001). In this study, 12.2% of patients in the sorafenib arm experienced tumor shrinkage of 30% or more compared with 0.5% of patients in the placebo arm (P
< .0001). An additional 41.8% of patients in the sorafenib arm achieved stable disease for at least 6 months, bringing the total disease control rate in the sorafenib arm to 54.1% compared with 33.8% in the placebo arm (P
< .0001). At the time the results were presented, overall survival data, a secondary endpoint, were not yet mature.
In this study, the most common any-grade, treatment-emergent adverse events observed in the sorafenib arm included hand-foot skin reaction, diarrhea, alopecia, rash/desquamation, fatigue, weight loss, and hypertension. One death in each arm was attributed to the study drug. Some patients also experienced anorexia, oral mucositis, pruritis, and nausea. In the sorafenib arm, 18.8% of patients discontinued treatment due to adverse events, compared with 3.8% of patients who received placebo.
Further analysis of this study is planned to identify biomarkers that could determine which patients are likely to relapse after surgery and RAI and are therefore more likely to benefit from treatment with sorafenib.
Brose MS, Nutting C, Jarzab B, et al. Sorafenib in locally advanced or metastatic patients with radioactive iodine-refractory differentiated thyroid cancer: The phase III DECISION trial. J Clin Oncol
. 2013;31(suppl; abstr 4).