A randomized phase III trial comparing trabectedin to best supportive care in patients with pre-treated soft tissue sarcoma: T-SAR, a French Sarcoma Group trial.

BACKGROUND The French Sarcoma Group assessed the efficacy, safety, and quality of life (QoL) of trabectedin vs best supportive care (BSC) in patients with advanced soft-tissue sarcoma (STS). PATIENTS AND METHODS This randomized, multicenter, open-label, phase III study included adults with STS who progressed after 1-3 prior treatment lines. Patients were randomized (1:1) to receive trabectedin 1.5 mg/m2 every three weeks or BSC, stratified into L-STS (lipo/leiomyosarcoma) and non-L-STS groups (other histotypes). Patients from BSC arm were allowed to cross over to trabectedin at progression. The primary efficacy endpoint was progression-free survival (PFS) confirmed by blinded central review and analyzed in the intention-to-treat population. RESULTS Between Jan 26, 2015, and Nov 5, 2015, 103 heavily pretreated patients (60.2% with L-STS) from 16 French centers were allocated to receive trabectedin (N=52) or BSC (N=51). Median PFS was 3.1 months (95% CI: 1.8-5.9) in the trabectedin arm vs 1.5 months (0.9-2.6) in the BSC arm (hazard ratio: 0.39, 95% CI: 0.24-0.64, P<0.001) with benefits observed across almost all analyzed subgroups, but particularly in patients with L-STS (5.1 vs 1.4 months, P=0.0001). Seven patients (13.7%) in the trabectedin arm (all with L-STS) achieved a partial response, while no objective responses were observed in the BSC arm (P=0.004). The most common grade 3/4 adverse events were neutropenia (44.2% of patients), leukopenia (34.6%), and transaminases increase (32.7%). Health-related EORTC QLQ-C30 QoL questionnaires evidenced no statistical differences between the arms for any domain and at any time point. After progression, 91.8% of patients crossed over from BSC to trabectedin. CONCLUSION Trabectedin demonstrates superior disease control to BSC without impairing QoL in patients with recurrent STS of multiple histologies, with greater impact in patients with L-STS.