Final overall survival analysis of patients with locally advanced or metastatic radioactive iodine-refractory differentiated thyroid cancer (RAI-rDTC) treated with sorafenib in the phase 3 DECISION trial: An exploratory crossover adjustment analyses

Background: The phase 3 DECISION trial (NCT00895674) met its primary endpoint of progression-free survival for patients with RAI-rDTC and showed a significant PFS prolongation in favor of sorafenib (SOR) vs placebo (PBO) (HR 0.587; p < 0.0001). Overall survival (OS) was immature at the time of primary analysis in Aug 2012. We report OS results from 9- and 36-months follow up with exploratory crossover adjustment analyses. Methods: Patients were randomized to SOR or PBO. PBO patients were allowed to receive SOR open-label (OL) upon progression. OS data were analyzed using 2 adjustment methods for crossover: iterative parameter estimation (IPE) and rank preserving structural failure time (RPSFT). For all analyses CIs were calculated with the Cox model and with bootstrapping to include additional variance originating from the crossover adjustment. Results: A total of 417 patients were randomized (207 SOR; 210 PBO). After progression, 158 of 210 patients (75%) crossed over to SOR. Hazard ratios (HRs) and 95% confidence intervals (CI) at the 3 data cutoffs are shown in the table. Although not significant, a consistent separation of the KM curves in favor of SOR was seen. OS crossover adjustment results showed larger treatment effects than ITT (ITT: 0.80-0.88; IPE : 0.70-0.80; RPSFT: 0.61-0.77). Conclusions: Due to the increasing effect of SOR in PBO patients over time, the separation between the 2 KM curves became smaller. Although significance was not reached in ITT, a trend in OS prolongation favoring SOR was observed consistently over successive time points. OS crossover adjustment results suggest that the true OS treatment effect may be larger than seen in the ITT analysis. The IPE method appears to produce more stable adjusted HRs across the 3 time points than RPSFT. These results should be considered as exploratory.(Table Presented).