Sorafenib in locally advanced or metastatic patients with radioactive iodine-refractory differentiated thyroid cancer: The phase III DECISION trial.

4 Background: Sorafenib, an orally active inhibitor of VEGFR1-3 and Raf kinases, has shown promising clinical activity in single-arm phase II studies in radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC). The double-blind, randomized, multicenter phase III DECISION trial examined sorafenib efficacy and safety vs placebo in patients with progressive RAI-refractory DTC.Patients with locally advanced/metastatic RAI-refractory DTC who progressed in the preceding 14 months were randomized 1:1 to sorafenib 400 mg bid po or placebo. Placebo patients were allowed to receive sorafenib open-label upon progression. The primary endpoint was progression-free survival (PFS) assessed every 8 wks by independent radiologic review using modified RECIST 1.0 and analyzed by stratified log-rank statistics at α = 0.01 (one-sided). Secondary endpoints included overall survival (OS), response rate (RR; complete + partial response [PR]), and safety.A total of 417 patients were randomized (207 to sorafenib and 210 to placebo); median age 63 yr, 52% female. Tumor histology by independent assessment was 57% papillary, 25% follicular, and 10% poorly differentiated. 96% of patients had metastatic disease; the most common target lesions were lung (71%), lymph node (40%), and bone (14%). The primary endpoint was met: median PFS 10.8 months (sorafenib) vs 5.8 months (placebo); HR 0.58, 95% CI 0.45-0.75, p<0.0001. Median OS has not been reached in either arm; 70% of placebo patients started open-label sorafenib. RR (all PRs) in the sorafenib vs placebo arms was 12.2% and 0.5% (p<0.0001) and stable disease ≥ 6 months was 42% and 33%, respectively. The most common any-grade treatment-emergent adverse events 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 study drug.Sorafenib significantly improved PFS compared with placebo in patients with progressive RAI-refractory DTC. Tolerability was consistent with the known sorafenib safety profile.NCT00895674.