The addition of trabectedin to doxorubicin did not demonstrate superiority over doxorubicin alone as first-line treatment for patients with advanced soft tissue sarcoma, a study published in the Journal of Clinical Oncology has shown.1
Doxorubicin has been considered an active drug in soft tissue sarcoma for many years; trabectedin was approved by the U.S. Food and Drug Administration (FDA) in 2015 for the treatment of 2 types of advanced soft tissue sarcoma. Because findings from a phase 1 trial showed that the combination is safe and preclinical research has suggested that it may be advantageous, researchers sought to compare the clinical outcome of trabectedin plus doxorubicin vs doxorubicin alone as first-line treatment of advanced soft tissue sarcoma.
For the open-label, phase 2 trial, researchers enrolled 115 patients and randomly assigned them to receive trabectedin 1.1 mg/m2 administered intravenously over 3 hours plus doxorubicin 60 mg/m2 intravenously or doxorubicin 75 mg/m2 alone. Participants received treatment for up to 6 cycles. Investigators also conducted translational research to identify correlates between apoptotic and DNA repair gene expression and clinical outcome.
Results showed that median progression-free survival was 5.7 with trabectedin plus doxorubicin compared with 5.5 months with single-agent doxorubicin (HR, 1.16; 95% CI, 0.79-1.71; P = .45). The trial was ultimately stopped early due to futility.
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Researchers also found that significantly more patients in the combination arm experienced grade 3 or 4 thrombocytopenia, asthenia, and hepatotoxicity than those in the monotherapy group.
In regard to biomarkers, apoptic key genes FAS and p53 were prognostic factors for progression-free survival and overall survival.
- Martin-Broto J, Pousa AL, de las Peñas R, et al. Randomized phase II study of trabectedin and doxorubicin compared with doxorubicin alone as first-line treatment in patients with advanced soft tissue sarcomas: A Spanish Group for Research on Sarcoma study [published online ahead of print May 16, 2016]. J Clin Oncol. doi: 10.1200/JCO.2015.65.3329.