Tumor growth rate analysis of progression-free survival (PFS) and overall survival (OS) for thyroid cancer patients receiving placebo or sorafenib in the phase 3 DECISION trial

Abstract

Background: In the randomized, controlled phase 3 DECISION trial (NCT00895674), sorafenib (SOR) significantly improved progression-free survival (PFS) vs placebo (PLC) in patients with radioactive iodine refractory differentiated thyroid cancer (HR, 0.587; p < 0.0001). Here we report the analysis exploring prognostic characteristics of tumor growth rate (TGR) for PFS and OS. Methods: The primary endpoint of DECISION was PFS and OS was a secondary endpoint. Target lesions were assessed by central radiologic review every 8 weeks based on RECIST 1.0 criteria. Changes in target lesions over time were approximated by a parabola-like 3-parametric model. TGR was defined as % change per month of sum of target lesion diameters (SLD). To explore the association between TGR and PFS and OS, values of early TGR were split into quartiles separately by treatment arm. PFS (cutoff in 2012) and OS (cutoff 2015) were compared in each subgroup population by median times derived from KM curves and from modeling with aWeibull distribution. Correlation of TGR with maximum reduction in SLDs was examined. Results: TGR subgroup statistics and median times of PFS and OS are shown in table 1. For these endpoints there is no simple proportional relation between TGR and median PFS or OS times. Better prognosis for PFS and OS is associated with Q2 or Q3 TGR quartiles. Early TGR values close to zero indicate a better prognosis. TGR and SLD show a high correlation. Conclusions: In this exploratory analysis, stabilization of tumor lesions at treatment start seems to be associated with better PFS and OS outcomes than a pronounced early reduction of tumor lesion sizes. TGR may be an additional efficacy parameter to consider when monitoring SOR treatment.(Table Presented).