A final analysis of a phase 2 trial led to recommending continuation of trabectedin for patients with advanced soft-tissue sarcoma (STS) who have not progressed after six courses of treatment. These results were published in The Lancet Oncology (2015; doi:10.1016/S1470-2045(15)70031-8).
The data indicate that continued treatment may be recommended for these patients, who received doxorubicin-based chemotherapy and are eligible for trabectedin, until treatment intolerance or disease. The acceptable and manageable safety profile and lack of cumulative toxicity of trabectedin was found to support this recommendation.
The trial found that continued therapy with trabectedin in these patients significantly improved progression-free survival (PFS) compared with treatment interruption. The results suggest not including a drug holiday in patients with advanced STS who benefit from trabectedin in terms of tumor control after six cycles of treatment. The safety profile was the same in both groups and as expected for patients treated with trabectedin.
“In the clinic, whether trabectedin should be given after six cycles in patients with advanced soft-tissue sarcoma who have not progressed during treatment was not clear, and the results of our study supports the maintenance of this therapy to achieve longer progression-free survival,” said lead investigator Nicolas Penel, MD, PhD, Department of Medical Oncology, Centre Oscar Lambret, France.
The study carried out at 14 centers of the French Sarcoma Group included 178 patients with advanced STS who were treated with six cycles of trabectedin (given at a dose of 1.5 mg/m2 for 24 hours every 3 weeks).
Of the 91 patients who were free of progression at the end of the treatment, 53 were then randomly assigned to continuously receive trabectedin or to drug interruption (although patients allocated to this group were allowed to restart trabectedin in cases of progressive disease).
The first clinical end point of the study was PFS after 6 months of the randomization, which was achieved by 51.9% of the patients in the continuation group versus 23.1% in the interruption group.
When PFS was measured at 12 months after randomization, a greater portion of patients in the continuation group were also progression-free compared to those who were not receiving trabectedin (33.3% versus 15.4%). This improvement in survival without progression was also supported by an increase in median PFS, which was 7.2 months (95% CI 4.0-12.7) in the continuation group and 4.0 months (95% CI 2.5-5.5) in the interruption group.
The study also showed how continuation of treatment with trabectedin in these patients was not associated with an increase in toxicity, suggesting that the safety profile of trabectedin is maintained after more than six cycles of treatment, and that this is accompanied by improved PFS.
Although the study has its limitations, as it was a noncomparative phase 2 trial, the investigators underscore that more than half of the patients in this setting treated with trabectedin were free of progression after six cycles of treatment and that early interruption of the drug results in worse PFS.