Results of the randomized phase III trial of trabectedin (T) versus doxorubicin-based chemotherapy (DXCT) as first-line therapy in patients (pts) with translocation-related sarcoma (TRS).

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10517 Background: T is the first of a new class of anticancer agents with a transcription-targeted mechanism of action. In vitro,T interferes with the aberrant transcription factors binding to DNA promoters in TRS. Methods: Pts with advanced TRS of the subtypes: myxoid liposarcoma (ML), alveolar soft part sarcoma, angiomatoid fibrous histiocytoma, clear cell sarcoma, desmoplastic small round cell tumor, low grade endometrial stromal sarcoma, low grade fibromyxoid sarcoma, myxoid chondrosarcoma and synovial sarcoma, stratified by performance status (0 vs 1-2) and subtype (ML vs other TRS) were randomized (1:1 ratio) to T (1.5 mg/m2 in 24h iv infusion q3wk) or doxorubicin, either single agent 75 mg/m2 q3wk, or 60 mg/m2 combined with ifosfamide (6-9 g/m2 q3wk) as 1st line treatment. Primary endpoint: efficacy of T vs DXCT by comparing progression-free survival (PFS). Secondary: PFS at 6 months (PFS6), response rate (RR), PFS/RR by subtype (ML vs other TRS); overall survival (OS), safety. Results: 121 pts enrolled from 22 centers, 88 were confirmed by central pathology review and evaluable for the primary efficacy endpoint by independent review assessment (IR), and all 121 pts randomized were evaluable by investigators’ assessment (IA). The main limitation of the study analyses in both arms was high censoring rate (70% IR; 61% IA) mostly due to surgery (~30%) or chemotherapy/ radiotherapy (~30%). PFS results are shown in the Table. PFS6 was not different between arms (IR: 66.4% vs 80.8% p=0.18/IA: 60.7% vs 62.4% p=0.88). Current median OS:not reached (NR) for T (24.1-NR) and 21.7 mo. for DXCT (21.2-NR).Safety: Most frequent AEs in both arms were nausea (70% vs 65%), vomiting (44% vs 26%) and fatigue (64% vs 63%). ALT increase G4 occurred in 10% pts treated with T and neutropenia G4 in 25% of pts in the T arm vs 52% in the DXCT arm. Conclusions: Although with a high censoring rate, this prospective study suggests thatPFS/OS with trabectedin are not significantly different from DXCT in first-line treatment. Clinical trial information: NCT00796120. [Table: see text]