Multicenter phase 3 trial of first-line doxorubicin-trabectedin with trabectedin maintenance in advanced leiomyosarcoma

A multicenter phase 3 trial in France evaluated first-line doxorubicin plus trabectedin, followed by trabectedin maitenance, in patients with metastatic or unresectable leiomyosarcoma who had not received chemotherapy previously. Patient were randomized to either six cycles doxorubicin or six cycles doxorubicin trabectedin with continued trabectedin as maintenance therapy in patients who did not have disease progression. Surgery to resect residual diseasewas allowed in each group after six cycles of therapy. Analyses of progression-free survival (primary endpoint) and overall survival (secondary endpoint) were adjusted for two stratification factors: tumor origin site (uterine versus soft tissue) and disease stage (locally advanced versus metastatic). Primary endpoint results were reported previously. At a median follow-up of 55 months, the median overall survival was 33 months in the doxorubicin-trabectedin group versus 24 months in the doxorubicin only group (aHR 0.65; 95% CI 0.44-0.95). Updated progression-free survival was 12 months versus 6 months (aHR 0.37; 95% CI 0.26-0.53). The incidence of adverse events and the percentage of patients with dose reductions were higher with doxorubicin plus trabedectin than with doxorubicin alone. The authors conclude that combiination therapy with doxxorubicin and trabedectin induction, followed by trabedectin maintenance, was associated with improved overall survival and progression-free survival, as compared with doxorubicin alone, among patients with metastatic or unresectable uterine or soft-tissue leiomyosarcoma.