演題抄録

臓器別シンポジウム

開催概要
開催回
第51回・2013年・京都
 

Phase 3 trial of sorafenib in RAI-refractory differentiated thyroid cancer

演題番号 : OS9-3

[筆頭演者]
Makoto Tahara:1 
[共同演者]
Marcia S Brose:2、Christopher Nutting:3、Young Kee Shong:4、Steven I Sherman:5、Johannes WA Smit:6、Istvan Molnar:7、Martin Schlumberger:8

1:Division of Head and Neck Medical Oncology, National Cancer Center Hospital East, Japan、2:The University of Pennsylvania, Abramson Cancer Center, Philadelphia, PA, USA、3:Royal Marsden Hospital, London, UK、4:Asan Medicine Center, University of Ulsan College of Medicine, Seoul, Korea、5:The University of Texas MD Anderson Cancer Center, Houston, TX, USA、6:Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands、7:Bayer HealthCare Pharmaceuticals, Montville, NJ, USA、8:Institut Gustave Roussy, Villejuif, France

 

Background: Sorafenib is an orally active inhibitor of VEGFR1-3 and Raf kinases with demonstrated clinical activity in the phase 2 setting in patients with radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC). We report here the results of a phase III trial (DECISION) comparing the safety and efficacy of sorafenib vs placebo in patients with progressive RAI-refractory DTC (NCT 00895674).
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. The primary endpoint was progression free survival (PFS) independently assessed every 8 weeks. Secondary endpoints included overall survival (OS), response rate (RR; complete + partial response [PR]), and safety. Placebo patients were allowed to receive sorafenib open-label upon progression.
Results: A total of 207 patients were randomized to sorafenib and 210 to placebo; median age 63 yr, 52% female. Tumor histology was 67% papillary, 24% follicular and 9% Hurthle cell. The most common target lesions were lung (71%), lymph node (40%) and bone (14%). The primary endpoint was met: median PFS sorafenib 10.8 months vs placebo 5.8 months; HR 0.587, 95% CI 0.454-0.758, p<0.0001. Median OS has not been reached in either arm; 71% 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 (76%), diarrhea (69%), alopecia (67%), rash/desquamation (50%), fatigue (50%), weight loss (47%), and hypertension (41%). 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. There were no unexpected toxicities.

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