Patients with advanced soft tissue sarcoma (STS), including both lipo-leiomyosarcoma and non lipo-leiomyosarcoma histotypes, who progressed despite prior therapies demonstrated prolonged progression-free survival (PFS) following trabectedin treatment compared to similar patients receiving best supportive care (BSC), according to phase III study results reported on 8 October at the ESMO 2016 Congress in Copenhagen, Denmark.
Although trabectedin has shown single-agent activity in patients with pretreated advanced STS and has been approved in Europe since 2007 for this indication, trabectedin had not been compared with BSC in a randomised trial comprising patients with all sarcoma histotypes, according to Axel Le Cesne, Department of Medicine, Institut Gustave Roussy, Villejuif, France.
Dr. Le Cesne and colleagues in the French Sarcoma Group assessed the efficacy, safety and quality of life of trabectedin versus BSC as a second or later treatment line in patients with advanced STS in the T-SAR trial.
T-SAR was a randomised, multicentre phase III trial that enrolled 103 adult patients ≥18 years of age with histologically proven advanced STS who progressed after at least one anthracycline-containing regimen but had received fewer than 3 previous chemotherapy lines. The patients were stratified according to lipo-leiomyosarcoma and non lipo-leiomyosarcoma status with ≥1 measurable baseline lesion (RECIST v.1.1); 60.2% of patients had lipo-leiomyosarcoma and 39.8% of patients had non lipo-leiomyosarcoma The patients had WHO performance status scores of 0 or 1, and were required to have adequate haematological and hepatic function.
The patients were randomised to either trabectedin (n=52) at 1.5 mg/m2 intravenously for 24 hours for 21 days (24h CI) and 51 to BSC until progressive disease (PD), unacceptable toxicity, or patient’s request. Crossover to trabectedin upon PD was allowed for patients receiving BSC. The primary endpoint was PFS, which was defined as time from randomisation to disease progression or all-cause death.
Significantly longer PFS was demonstrated with trabectedin. After 88 cases of PD were observed the data were evaluated for PFS. The median PFS from randomisation was doubled with trabectedin; median PFS was 3.12 months with trabectedin compared with 1.51 months with BSC, hazard ratio (HR) 0.39; 95% confidence interval (CI) 0.26, 0.63 (p < 0.0001).
Patients with lipo-leiomyosarcoma showed greater benefit from trabectedin; median PFS was 5.13 months with trabectedin versus 1.4 months with BSC, HR 0.29; 95% CI 0.15, 0.55 (p < 0.0001). In the non lipo-leiomyosarcoma cohort the median PFS was 1.81 versus 1.51 months with trabectedin versus BSC, respectively, HR 0.60; 95% CI 0.29, 1.26 (p = 0.18).
The authors concluded that the pre-planned PFS analysis in this study demonstrated a significant improvement in median PFS with trabectedin over BSCin patients with pretreated advanced STS of multiple histologies, thereby meeting the primary endpoint of the study.
A major impact of trabectedin was observed in the lipo-leiomyosarcoma STS cohort (median PFS in the BSC and trabectedin arm were 1.4 month and 5.13 month (HR: 0.29, p < 0.0001), respectively), whereas in the non lipo-leiomyosarcoma STS group the median PFS were 1.51 month and 1.8 month (statistically non-significant difference).
Results of a prospective randomized phase III T-SAR trial comparing trabectedin vs best supportive care (BSC) in patients with pretreated advanced soft tissue sarcoma (ASTS)
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.L. Ray-Coquard, O. Mir, L. Haddag, S. Foulon
This study was funded by PharmaMar.