A retrospective analysis of antitumour activity with trabectedin in translocation-related sarcomas

Aims: Approximately 20% of soft tissue sarcomas (STS) have subtype-specific chromosomal translocations; these generate chimeric oncoproteins which can act as abnormal transcription factors. Since trabectedin can bind to DNA and displace transcription factors, antitumour activity was explored in translocation-related sarcoma (TRS) subtypes. Methods: The current retrospective pooled analysis includes data from 81 patients with TRS treated in 8 phase II trials. Results: TRS subtypes were: synovial sarcoma (SS, n = 45), myxoid-round cell liposarcoma (MRC-L-sarcoma, n = 27), alveolar soft part sarcoma (ASPS, n = 4), endometrial stromal sarcoma (ESS, n = 3) and clear cell sarcoma (CCS, n = 2). All but one patient had received prior chemotherapy (median of 2 lines). Patients received a median of 4 trabectedin cycles (range, 1-48; median dose intensity = 0.40 mg/m²/week). Partial responses according to Response Evaluation Criteria in Solid Tumours (RECIST) occurred in 8 patients (ORR = 10%; 95% CI, 4-19%): four in MRC-L-sarcoma; three in SS and one in ESS. Tumour control rate (ORR plus stable disease) was 59% (95% CI, 48-70%). Median PFS was 4.1 months (6-month PFS rate = 40%). Median overall survival was 17.4 months (survival rate at 12 months = 60%). Trabectedin had a manageable safety profile. Conclusion: Trabectedin demonstrates encouraging disease control in TRS. Since these promising results were generally noted in patients following chemotherapy, a phase III randomised trial in first-line is ongoing to compare trabectedin with doxorubicin-based chemotherapy in patients with TRS.