Background
Phase 3 RCT of 518 patients (2:1 randomization) with advanced liposarcoma or leiomyosarcoma after prior anthracycline and at least one additional systemic regimen, comparing trabectedin with dacarbazine.
Interventions and follow up
Arm A: Trabectedin 1.5 mg/m2 as a 24-hour IV infusion q3wk
Arm B: Dacarbazine 1 g/m2 as a 20-120 min IV infusion q3wk
Primary endpoint: Overall survival
Secondary endpoints: PFS, ORR, DoR, safety
mFollow up: 21.2 mo (PFS analysis 8.6 mo)
Arm B: Dacarbazine 1 g/m2 as a 20-120 min IV infusion q3wk
Primary endpoint: Overall survival
Secondary endpoints: PFS, ORR, DoR, safety
mFollow up: 21.2 mo (PFS analysis 8.6 mo)
Results
mPFS: 4.2 mo vs 1.5 mo; HR 0.55, 95%CI 0.44-0.70, P<.001
ORR: 9.9% vs 6.9%, P=.33; no CR in either arm
Median DoR: 6.5 mo vs 4.2 mo, P=.14
Stable disease: 51% vs 35%
mOS: 12.4 mo vs 12.9 mo; HR 0.87, 95%CI 0.71-1.05, P=.37 (NS at final analysis)
ORR: 9.9% vs 6.9%, P=.33; no CR in either arm
Median DoR: 6.5 mo vs 4.2 mo, P=.14
Stable disease: 51% vs 35%
mOS: 12.4 mo vs 12.9 mo; HR 0.87, 95%CI 0.71-1.05, P=.37 (NS at final analysis)
Adverse events
Grade 4 hematologic: neutropenia 16% vs 10%, thrombocytopenia 9% vs 8%
Grade 3 hematologic: neutropenia 21% vs 11%, anemia 14% vs 11%
Grade 3 hepatic: increased ALT 25% vs 1%, increased AST 12% vs 0%
Grade 3 hematologic: neutropenia 21% vs 11%, anemia 14% vs 11%
Grade 3 hepatic: increased ALT 25% vs 1%, increased AST 12% vs 0%
Conclusions
Trabectedin significantly improved progression-free survival and disease control over dacarbazine in advanced liposarcoma or leiomyosarcoma after anthracycline failure, without a significant OS difference, supporting it as an effective later-line option.
Key Limitations
Primary OS endpoint was not met; benefit limited to PFS/disease control. Dacarbazine is a modest comparator. Restricted to L-sarcoma histologies, limiting generalizability to other soft-tissue sarcomas.
Clinical Context
Supported FDA approval (Oct 2015) of trabectedin for unresectable/metastatic liposarcoma or leiomyosarcoma after anthracycline-containing therapy; ESMO recognizes trabectedin as a standard later-line option, particularly in L-sarcomas.