CHICAGO—Sorafenib represents a potential new treatment option for patients with locally advanced or metastatic radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), results of the first phase 3 study of a targeted agent in this disease reported in a presentation at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting.
Patients treated with sorafenib in the DECISION trial had a significantly improved progression-free survival (PFS), the primary endpoint, with the multi-kinase inhibitor extending median PFS by 5 months compared with placebo, said Marcia S. Brose, MD, PhD, of the Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia, PA. This represents the first therapeutic advance for patients with thyroid cancer in 40 years.
The study randomly assigned 417 patients with RAI-refractory DTC with disease progression within the previous 14 months and no prior chemotherapy, targeted therapy, or thalidomide to sorafenib 400 mg orally twice daily (n=207) or placebo (N=210). At disease progression, patients in the placebo arm were allowed to cross over to the sorafenib arm.
Median patient age was 63 years; 52% were female. Tumor histology was 57% papillary, 25% follicular, and 10% poorly differentiated; 96% of patients had metastatic disease, with the most common target lesions being lung (71%), lymph node (40%), and bone (14%).
Results showed median PFS was 10.8 months in the sorafenib arm versus 5.8 months in the placebo arm (hazard ratio [HR], 0.587; 95% CI: 0.454-0.758; P<0.0001). Median overall survival was not reached in either arm. At disease progression, 150 patients (71%) on placebo received open-label sorafenib, as did 55 patients (27%) on sorafenib.
Response rate was 12.2% in the sorafenib arm compared with 0.5% in the placebo arm (P<0.0001), all parti al responses, with a median duration of response of 10.2 months (range, 7.4-16.6 months). An additional 41.8% of patients in the sorafenib arm had stable disease for 6 months or longer, for a disease control rate of 54.1%, compared with a disease control rate of 33.8% in the placebo arm (P<0.0001).
Safety results were consistent with the known safety profile of sorafenib, Dr. Brose noted. The most frequent adverse events were hand-foot skin reaction, diarrhea, alopecia, rash/desquamation, fatigue, and hypertension. There was one treatment-related death in each arm.
Future studies will address DTC refractory to vascular endothelial growth factor receptor inhibition.
This research was supported in part by Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals.