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

Head and Neck Cancer
Session Type and Session Title: 
Plenary Session, Plenary Session Including FDA Commissioner Address, Public Service Award, and Science of Oncology Award and Lecture
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr 4)
Marcia S. Brose, Christopher Nutting, Barbara Jarzab, Rossella Elisei, Salvatore Siena, Lars Bastholt, Christelle de la Fouchardiere, Furio Pacini, Ralf Paschke, Young Kee Shong, Steven I. Sherman, Johannes WA Smit, John Woojune Chung, Harald Siedentop, Istvan Molnar, Martin Schlumberger; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA; The Royal Marsden NHS Foundation Trust, London, United Kingdom; Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; Azienda Ospedaleria Niguarda Ca' Granda, Milano, Italy; Odense University Hospital, Odense, Denmark; Consortium Cancer Thyroïdien, Hospices Civils-Centre Anticancéreux, Lyon, France; Unit of Endocrinology, University of Siena, Siena, Italy; Department for Endocrinology and Nephrology, Leipzig University, Leipzig, Germany; Asan Medicine Center, University of Ulsan College of Medicine, Seoul, South Korea; The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Internal Medicine, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands; Bayer HealthCare Pharmaceuticals, Montville, NJ; Bayer Pharma AG, Berlin, Germany; Institut Gustave Roussy, Villejuif, France

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Abstract Disclosures


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. Methods: 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. Results: 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. Conclusions: Sorafenib significantly improved PFS compared with placebo in patients with progressive RAI-refractory DTC. Tolerability was consistent with the known sorafenib safety profile. Clinical trial information: NCT00895674.