For the first time in decades, a drug has halted disease progression in treatment-resistant differentiated thyroid cancer, according to the results of a phase III study presented at the 2013 ASCO Annual Meeting.1
No new drugs have been approved for differentiated thyroid cancer in 40 years, but this could soon change. In patients with the disease who were refractory to radioactive iodine therapy, sorafenib (Nexavar) significantly prolonged progression-free survival by 5 months, reported Marcia Brose, MD, PhD, Assistant Professor of Otolaryngology and Head and Neck Surgery at the University of Pennsylvania Perelman School of Medicine, Philadelphia.
DECISION Trial
“DECISION is the first phase III study of a targeted agent in radioactive iodine–refractory differentiated thyroid cancer, which is a rare condition with a poor prognosis and no effective standard treatment,” Dr. Brose said. “Sorafenib is a potential new treatment option for these patients.”
Differentiated thyroid cancer is the most common subtype of thyroid cancer, with an estimated 60,000 new cases a year and 1,850 related deaths. While most patients can be cured by surgery and radioactive iodine, many patients require repeated radioactive iodine treatments, and 5% to 15% develop resistance to it. In this subset, median survival is around 2.5 to 3.5 years and disease-related complications are common, she said.
The fact that the 89-center study rapidly enrolled hundreds of patients “speaks to the unmet needs of these patients,” she said.
Progression-free Survival Improvement
DECISION was a randomized, double-blind, placebo-controlled phase II trial in which 417 patients with radioactive iodine–refractory, locally advanced or metastatic differentiated thyroid cancer were randomly assigned to sorafeninb, 400 mg twice daily, or placebo until disease progression. Sorafenib was available to nonresponding placebo recipients in the open-label component of the trial.
Median progression-free survival was 10.8 months in the sorafenib arm vs 5.8 months in the placebo arm (hazard ratio = 0.587; P < .0001).
Response by RECIST criteria was observed in 12.2% of the sorafenib arm vs 0.5% of the placebo arm (P < .0001). Stable disease was observed in an additional 41.8% of patients receiving sorafenib, vs 33.2% with placebo, reflecting disease control rates of 54.1% and 33.8%, respectively (P < .0001). The median duration of response to sorafenib was 10.2 months.
Median overall survival has not been reached in either arm, but there is currently a 20% non–statistically significant reduction in mortality with sorafenib, despite a 71% rate of crossover to sorafenib.
The adverse event profile was similar to the known toxicity profile for the multi–tyrosine kinase inhibitors. Serious adverse events were observed in 37.2% of the sorafenib arm and 26.3% of the placebo arm, including secondary malignancies (4.3% vs 1.9%), pleural effusion (2.9% vs 1.9%), and dyspnea (3.4% vs 2.9%). One drug-related grade 5 event occurred in each arm. Dose modifications due to adverse events were necessary in 77.8% and 30.1%, respectively, and permanent discontinuations due to toxicity were seen in 18.8% and 3.8%, respectively. ■
Disclosure: Dr. Brose has served in a consultant or advisory role for Bayer and Onyx, and has received honoraria or research funding from Bayer.
Reference
1. 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. 2013 ASCO Annual Meeting. Abstract 4. Presented June 2, 2013.
