Sorafenib in locally advanced or metastatic, radioactive iodine-refractory, differentiated thyroid cancer: a randomized, double-blind, phase 3 trial
By M. Brose, C. Nutting, B. Jarzab, R. Elisei, S. Siena, L. Bastholt, C. de la Fouchardière, F. Pacini, R. Paschke, Young KeeShong and 7 more. The Lancet, 2014
1,337 citations recorded by the source corpus.
Background Patients with radioactive iodine (131I, RAI)-refractory locally advanced or metastatic differentiated thyroid cancer (DTC) have a poor prognosis due to the lack of effective treatment options. Methods This multicentre, randomized (1:1), double-blind, placebo-controlled, phase 3 study (DECISION; NCT00984282) investigated sorafenib (400 mg orally twice-daily) in patients with RAI-refractory locally advanced or metastatic DTC progressing within the past 14 months. The primary endpoint was progression-free survival (PFS) by central independent review. Patients receiving placebo could crossover to open-label sorafenib upon progression. Archival tumour tissue was examined for BRAF and RAS mutations. Serum thyroglobulin was measured at baseline and each visit. Findings A total of 417 patients were randomized to sorafenib (n=207) or placebo (n=210). Sorafenib treatment significantly improved PFS compared with placebo (hazard ratio, 0·59; 95% confidence interval, 0·45–0·76; P<0·0001; median 10·8 vs. 5·8 months, respectively). PFS improvement was seen in all pre-specified clinical and genetic biomarker subgroups irrespective of mutation status. There was no statistically significant difference in overall survival (hazard ratio, 0·80; 95% confidence interval, 0·54–1·19; P=0·14); median overall survival had not been reached and 150 (71%) patients receiving placebo crossed over to sorafenib upon progression. Response rates (all partial responses) were 12·2% (24/196; sorafenib) and 0·5% (1/201; placebo; p<0·0001). Median thyroglobulin levels increased in the placebo group, and decreased, then paralleled treatment responses in the sorafenib group. Most adverse events were grade 1 or 2. The most common treatment-emergent adverse events in the sorafenib arm were hand–foot skin reaction (76·3%), diarrhoea (68·6%), alopecia (67·1%), and rash/desquamation (50·2%). Interpretation Sorafenib significantly improved PFS compared with placebo in patients with progressive RAI-refractory DTC. Adverse events were consistent with the known sorafenib safety profile. These results suggest that sorafenib represents a new treatment option for patients with progressive RAI-refractory DTC.
Subfields: Endocrinology, Diabetes and Metabolism, Surgery
View Paper: https://www.semanticscholar.org/paper/61cd584854310a0cdb2e3364a61f638aca7d1c8a
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Citations in the corpus
- Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer (2015, background): “The pediatric experience has been limited to published case reports and anecdotal clinical experience, primarily with sorafenib (353,354), which is FDAapproved for the treatment of advanced iodine-refractory DTC in adults based upon the results of a phase III trial (355).”
- 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: What is new and what has changed? (2017, neutral): “There have been several impressive advances in the management of patients with advanced and RAI-refractory DTC over the past 5 to 10 years.(34-38) Unfortunately, the majority of the recommendations in this section are weak recommendations based on low-quality evidence, a finding that demonstrates th”
- 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer (2009, positive): “In each of two recent international, randomized phase III trials of kinase inhibitors for therapy of progressive, RAIrefractory, metastatic DTC, patients whose tumors contained the BRAF mutation who were randomized to the placebo treatment arms experienced similar progression-free survival compared ”
- Ten years of anti-vascular endothelial growth factor therapy (2016, background): “Sorafenib was also approved for the treatment of advanced hepatocellular carcinoma 112 in November 2007 and thyroid cancer 113 in November 2013.”
- Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. (2019, background): “[96]: hand-and-foot skin reactions, diarrhoea, alopaecia, rash or desquamation, fatigue, weight loss and hypertension were the most common.”