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Bending the Curve Trial by Trial
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DECISION

A Double-Blind Randomized Phase III Study Evaluating the Efficacy and Safety of Sorafenib Compared to Placebo in Locally Advanced/Metastatic RAI-Refractory Differentiated Thyroid Cancer

Phase 3N = 417NCT00984282

Population
Adults with radioactive iodine-refractory locally advanced or metastatic differentiated thyroid cancer that had progressed within the past 14 months, with at least one measurable lesion by RECIST, ECOG performance status 0 to 2 and serum TSH below 0.5 mIU/L
Design
Multicentre, randomised (1:1), double-blind, placebo-controlled phase 3 trial of sorafenib 400 mg twice daily versus matching placebo, run at 77 centres in 18 countries. Primary end point progression-free survival, assessed every 8 weeks by central independent review. Placebo patients could cross over to open-label sorafenib at progression.
Primary endpoint
PFS
Arms
  • Sorafenib (experimental, n = 207): Sorafenib 400 mg orally twice daily
  • Placebo (control, n = 210): Matching placebo
People
Brose MS
PFSHR 0.59 (95% CI 0.45–0.76)Δ median PFS+5 monthsOSHR 0.80 (95% CI 0.54–1.19)Δ ORR+11.7 points
Show the numbers
Results reported for DECISION
EndpointAnalysisSorafenibPlaceboEffect
PFSITT (417 patients: 207 sorafenib, 210 placebo)primaryBrose 2014median 10.8 monthsmedian 5.8 monthsHR 0.59 (95% CI 0.45–0.76)P<0.0001Progression-free survival was assessed by central independent review. The abstract states improvement in all prespecified clinical and genetic biomarker subgroups, irrespective of mutation status.
OSRandomised patients (417: 207 sorafenib, 210 placebo)primaryBrose 2014——HR 0.80 (95% CI 0.54–1.19)P=0.14No statistically significant difference in overall survival; median overall survival had not been reached at the primary analysis. 150 of 210 placebo patients (71.4%) crossed over to open-label sorafenib at progression, which may confound the comparison (authors' statement).
ORRPatients with response data as reported (196 sorafenib, 201 placebo)primaryBrose 201412.2%0.5%P<0.0001Objective response rate was a secondary end point; all responses were partial responses (24 of 196 with sorafenib, 1 of 201 with placebo).
Results reported for DECISION
EndpointAnalysisSorafenibPlaceboEffect
PFSITT (417 patients: 207 sorafenib, 210 placebo)primaryBrose 2014median 10.8 monthsmedian 5.8 monthsHR 0.59 (95% CI 0.45–0.76)P<0.0001Progression-free survival was assessed by central independent review. The abstract states improvement in all prespecified clinical and genetic biomarker subgroups, irrespective of mutation status.
OSRandomised patients (417: 207 sorafenib, 210 placebo)primaryBrose 2014——HR 0.80 (95% CI 0.54–1.19)P=0.14No statistically significant difference in overall survival; median overall survival had not been reached at the primary analysis. 150 of 210 placebo patients (71.4%) crossed over to open-label sorafenib at progression, which may confound the comparison (authors' statement).
ORRPatients with response data as reported (196 sorafenib, 201 placebo)primaryBrose 201412.2%0.5%P<0.0001Objective response rate was a secondary end point; all responses were partial responses (24 of 196 with sorafenib, 1 of 201 with placebo).
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS0.590.45–0.76
OS0.80.54–1.19
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%0510152025Months (modelled)
  • Sorafenib (experimental)
  • Placebo (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsSorafenibPlacebo
0100.0%100.0%
763.8%43.3%
1440.7%18.8%
2027.7%9.2%
2717.7%4.0%
Primary publication: Brose MS, Nutting CM, Jarzab B, Elisei R, Siena S, Bastholt L, et al. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet. 2014;384(9940):319-28. PubMedDOI

Appears in

Sources

  1. Brose MS, Nutting CM, Jarzab B, Elisei R, Siena S, Bastholt L, et al. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet. 2014;384(9940):319-28.

    PubMedDOI