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
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.
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).
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.
|Database cutoff||HR (Cox model 95% CI) (bootstrapping 95% CI )|
|2012 Aug||0.80 (0.54–1.19) (0.53, 1.18)||0.70 (0.47–1.04) (0.40, 1.38)||0.61 (0.40–0.94) (0.18, 2.16)|
|2013 May||0.88 (0.63–1.24) (0.63, 1.25)||0.79 (0.57–1.11) (0.46, 1.61)||0.69 (0.49–0.99) (0.33, 1.65)|
|2015 Jul||0.92 (0.71–1.21) (0.71, 1.21)||0.80 (0.61–1.05) (0.48, 1.71)||0.77 (0.58–1.02) (0.42, 1.79)|
*Unadjusted for treatment switch
Clinical trial identification
Legal entity responsible for the study
Bayer Healthcare Pharmaceuticals
M. Brose: Received consultancy fees/honorarium and research support from Bayer HealthCare Pharmaceuticals; consultancy fees and research support from Exelixis; consultancy fees from Onyx Pharmaceuticals; and research support from Eisai, Novartis, & Roche/Genentech. B. Jarzab: Received honorarium and research support from Bayer Healthcare Pharmaceuticals; consultancy fees/honorarium from AstraZeneca and Sobi; and honorarium from Eisai, Ipsen, Novartis, OxiGene, Pfizer, Roche, and Sanofi. R. Elisei: Consultancy fees/honorarium and research support from Bayer Healthcare Pharmaceuticals; and consultancy fees/honorarium from AstraZeneca and Genzyme. L. Bastholt: Consultancy fees and research support from Bayer Healthcare Pharmaceuticals; and consultancy fees from AstraZeneca. C. de la Fouchardiere: Consultancy fees/honorarium and research support from Bayer Healthcare Pharmaceuticals; consultancy feels from AstraZeneca, Sanofi-Aventis, and Sobi; and a grant from Roche. F. Pacini: Honorarium and research support from Bayer Healthcare Pharmaceuticals. R. Paschke: Research support from Bayer Healthcare Pharmaceuticals. S. Sherman: Research support from Bayer Healthcare Pharmaceuticals, Genzyme, and Pfizer; consultancy fees/honorarium and research support from Amgen; consultancy fees/honorarium from AstraZeneca, Eisai, Exelixis, Lilly, NovoNordisk, Veracyte, Onyx, and Roche. J. Smit: Member of the DECISION steering committee and has received honorarium and research support from Bayer Healthcare Pharmaceuticals. J. Chung, G. Meinhardt: Employee of Bayer Healthcare Pharmaceuticals. M. Schlumberger: Received consultancy fees and research support from Bayer Healthcare. Pharmaceuticals and Eisai; consultancy fees/honorarium and research support from AstraZeneca and Genzyme-Sanofi; consultancy fees from Exelixis; and consultancy fees/honorarium from Sobi. C. Kappeler: Employee of Bayer Pharma AG. All other authors have declared no conflicts of interest.