A retrospective analysis of antitumour activity with trabectedin in translocation-related sarcomas
Axel Le Cesne1, Sara Cresta, Robert G Maki
1Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France. lecesne@igr.fr.
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/m(2)/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.
Insights
Trabectedin shows promising disease control in translocation-related sarcomas (TRS), a rare cancer subtype. Further research is ongoing to compare its effectiveness against standard chemotherapy in initial treatment settings.
Area of Science:
- Oncology
- Medical Research
- Pharmacology
Background:
- Soft tissue sarcomas (STS) comprise a heterogeneous group of cancers, with approximately 20% exhibiting specific chromosomal translocations.
- These translocations result in chimeric oncoproteins that function as aberrant transcription factors, driving tumor development.
- Trabectedin's mechanism involves DNA binding and displacement of transcription factors, suggesting potential efficacy in translocation-related sarcomas (TRS).
Purpose of the Study:
- To explore the antitumour activity of trabectedin in patients with translocation-related sarcoma (TRS) subtypes.
- To evaluate the efficacy and safety of trabectedin in a heavily pre-treated patient population with TRS.
Main Methods:
- A retrospective pooled analysis of data from 81 patients with TRS across 8 phase II clinical trials.
- Patients received trabectedin treatment, with data analyzed for response rates, tumor control, progression-free survival (PFS), and overall survival (OS).
Main Results:
- The study included various TRS subtypes, predominantly synovial sarcoma (SS) and myxoid-round cell liposarcoma (MRC-L-sarcoma).
- Trabectedin demonstrated an objective response rate (ORR) of 10% and a tumor control rate of 59%.
- Median PFS was 4.1 months, and median overall survival was 17.4 months, with a manageable safety profile.
Conclusions:
- Trabectedin exhibits encouraging disease control in translocation-related sarcomas (TRS), even in patients with prior chemotherapy exposure.
- These findings support ongoing phase III trials comparing trabectedin with doxorubicin-based chemotherapy as a first-line treatment for TRS.
