Exp Clin Endocrinol Diabetes 2014; 122 - OP7_36
DOI: 10.1055/s-0034-1372011

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

A Bockisch 1, MS Brose 2, C Nutting 3, B Jarzab 4, R Elisei 5, S Siena 6, L Bastholt 7, C de la Fouchardiere 8, F Pacini 9, R Paschke 10, YK Shong 11, SI Sherman 12, JW Smit 13, JW Chung 14, C Kappeler 15, I Molnar 14, M Schlumberger 16
  • 1University Hospital Essen, Nuclear Medicine, Essen, Germany
  • 2University of Pennsylvania, Pensylvania, United States
  • 3The Royal Marsden NHS Foundation Trust, London, United Kingdom
  • 4Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland
  • 5University of Pisa, Department of Clinical and Experimental Medicine, Pisa, Italy
  • 6Azienda Ospedaleria Niguarda Ca' Granda, Milano, Italy
  • 7Odense University Hospital, Odense, Denmark
  • 8Hospices Civils-Centre Anticancéreux, Consortium Cancer Thyroïdien, Lyon, France
  • 9University of Siena, Unit of Endocrinology, Siena, Italy
  • 10Leipzig University, Department for Endocrinology and Nephrology, Leipzig, Germany
  • 11University of Ulsan College of Medicine, Asan Medicine Center, Seoul, Korea, Republic of
  • 12The University of Texas, MD Anderson Cancer Center, Houston, United States
  • 13Radboud University Nijmegen Medical Center, Department of Internal Medicine, Nijmegen, Netherlands
  • 14Bayer HealthCare Pharmaceuticals, Whippany, United States
  • 15Bayer Pharma AG, Berlin, Germany
  • 16Institut Gustave Roussy, Villejuif, France

Introduction: Sorafenib (SO), 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 DTC. The double-blind, randomized, multicenter phase III DECISION trial examined SO efficacy and safety vs. placebo (PL) in patients (pts) with progressive RAI-refractory DTC.

Methods: Pts with locally advanced/metastatic RAI-refractory DTC who progressed in the preceding 14 months were randomized 1: 1 to SO 400 mg bid po or PL. PL pts were allowed to receive SO 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: overall survival (OS), response rate (RR; complete + partial response [PR]), and safety.

Results: 417 pts were randomized (207 to SO, 210 to PL); median age 63 yr, 52% female. Tumor histology by independent assessment was 56% papillary, 25% follicular, 9% poorly differentiated. 96% of pts had metastatic disease; the most common metastatic lesions were lung (86%), lymph node (51%), bone (27%). The primary endpoint was met: median PFS 10.8 months (SO) vs. 5.8 months (PL); HR 0.587, 95% CI 0.45 – 0.75, p < 0.0001. Median OS has not been reached in either arm; 71% of PL pts started open-label SO. RR (all PRs) in the SO vs. PL 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 SO 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 pts with progressive RAI-refractory DTC. Tolerability was consistent with the known sorafenib safety profile. Clinical trial information: NCT00895674.