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

SUMMARY: The FDA approved Sorafenib (NEXAVAR®) for the treatment of patients with locally recurrent or metastatic, progressive, Differentiated Thyroid Carcinoma (DTC), refractory to RadioActive Iodine (RAI) treatment. Over 90% of all thyroid cancers are classified as Differentiated Thyroid Cancers with Papillary, Follicular and Hürthle cell histologies. NEXAVAR® inhibits multiple kinases that are involved in cell proliferation and angiogenesis thereby preventing cancer growth. These kinases include Raf, VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-B, KIT, FLT-3 and RET. The DECISION trial is a randomized, double-blind, multicenter phase III study in which the efficacy and safety of NEXAVAR® was compared with placebo, in patients with progressive RAI-refractory DTC. Four hundred and seventeen patients (417) were randomized to receive either NEXAVAR® 400 mg po BID (n=207) or placebo (n=210). The median age was 63 yrs and only patients who had no prior chemotherapy or targeted therapy and with disease progression within the preceding 14 months, were included. Over 95% of the patients had metastatic disease and the most common sites of spread were lungs and lymph nodes. Treatment was continued until disease progression or until unacceptable toxicity was noted. Upon progression, patients in the placebo group were allowed to crossover and receive open-label NEXAVAR®. The primary endpoint was Progression Free Survival (PFS). Secondary endpoints included Overall Survival (OS), Response Rate (RR=Complete + Partial Response [PR]), and safety. Approximately 70% of patients in the placebo arm were allowed to crossover to receive open-label NEXAVAR®. The median PFS was 10.8 months with NEXAVAR® compared to 5.8 months with placebo (hazard ratio [HR] = 0.58; P <0.0001). Partial responses were observed in 12.2% of patients receiving NEXAVAR® compared with 0.5% in the placebo arm (P < 0.0001). Further, 42% of patients in the NEXAVAR® group had stable disease for 6 months or more compared to 33% in the placebo group. Median OS has not been reached. The most common adverse events in the NEXAVAR® group included hand–foot skin reaction, diarrhea, rash/desquamation, fatigue and hypertension. The authors concluded that NEXAVAR® extends PFS in a select group of patients with advanced DTC and is the first and only FDA approved therapy for DTC. Brose MS, Nutting C, Jarzab B, et al. J Clin Oncol 31, 2013 (suppl; abstr 4)