Impact of regorafenib treatment on overall survival (OS) in advanced sarcoma patients.

11556 Background: Regorafenib has been evaluated in several sarcoma clinical trials and the common primary endpoint of these studies was Progression-Free Survival (PFS) according to RECIST, with OS as secondary endpoint. We aimed to assess the impact of regorafenib on OS using pooled analysis of REGOSARC (NCT01900743, five cohorts: liposarcoma, leiomyosarcoma, synovial sarcoma, other soft tissue sarcoma and non-adipocytic sarcoma post-pazopanib) and (NCT02389244, four cohorts: osteosarcoma, Ewing sarcoma, chondrosarcoma and chordoma). Both trials were placebo-controlled trials with potential switch to regorafenib in placebo-arm at progression. Methods: The primary endpoint was OS in months (mo.) from randomisation estimated by Kaplan-Meier method. The Hazard Ratio (HR) of death in a Cox model was stratified by histological . We used 2 methods for controlling regorafenib switch on OS: Rank-Preserving Structural Failure Time Model (RPSFTM; White et al. 1997) and Modified Iterative Parametric Estimation (MIPE: Zhang et al. 2016), with bootstrap-based 95%CI for both methods. Two populations were considered: in the primary analysis included all patients in both trials (n=355), and in secondary analysis excluded chordoma and liposarcoma patients (n=289), since regorafenib failed to demonstrate activity in these subtypes. Results: In primary analysis, the median age was 56.0 years (range, 16.0; 85.0); 325 patients (91.5%) had metastatic disease. 218 (61.4%) patients had soft tissue sarcoma and 137 (38.6%) patients had bone sarcoma. Median follow-up was 70.9 mo (IQR: 54.0-87.5). The median OS was 9.5 mo. (95%CI, 7.7-12.4) in Placebo arm versus 12.8 mo. (95%CI, 11.0-15.8) in regorafenib arm (HR: 0.85 (95%CI, 0.67-1.06); p=0.148). When correcting regorafenib switch effect, the estimated HR was 0.59 (0.31-1.25) and 0.62 (0.27-1.46) using RPSFTM and MIPE methods, respectively. Conclusions: In this pooled analysis, we observe a marked difference in OS, but which does not reach the , even after exclusion of chordomas and liposarcomas patients (20%-risk reduction, with p=0.083). After controlling for the switch effect, the corrected effect of regorafenib increased dramatically from 20% risk-reduction of death to a 45%-50% reduction in the population excluding chordomas and liposarcomas.