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.

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).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.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.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.


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Authors: A Le Cesne, J-Y Blay, D Cupissol, A Italiano, C Delcambre, N Penel, N Isambert, C Chevreau, E Bompas, F Bertucci, L Chaigneau, S Piperno-Neumann, S Salas, M Rios, C Guillemet, J-O Bay, I Ray-Coquard, L Haddag, J Bonastre, R Kapso, A Fraslin, N Bouvet, O Mir, S Foulon, French Sarcoma Group