Trabectedin added to doxorubicin in advanced leiomyosarcoma

A new phase III study, recently published on The New England Journal of Medicine, showed that a first-line treatment with doxorubicin and trabectadine, followed by trabectadin maintenance, improved overall and progression free survival in patients with metastatic or surgically unresectable uterine or soft-tissue leiomyosarcoma.

Leiomyosarcomas account for nearly one quarter of all soft-tissue sarcomas, which occur predominantly in uterine locations and are characterised by not so favourable prognosis in metastatic or locally advanced stages. Doxorubicin monotherapy is the standard first-line treatment since 50 years, but combination therapy with trabectedin showed promising results in a phase II trial. In this phase III study authors involved a total of 150 patients with metastatic or unresectable leiomyosarcoma who had not received chemotherapy previously, randomizing them to receive either single-agent doxorubicin (six cycles) or doxorubicin plus trabectedin (six cycles), with continued trabectedin as maintenance therapy in patients in the doxorubicin–trabectedin group who did not have disease progression. At a median follow-up of 55 months the median overall survival was longer in the doxorubicin–trabectedin group (33 months) than in the doxorubicin group (24 months); progression-free survival was longer in the doxorubicin–trabectedin group (12 months) than in the doxorubicin group (6 months). The incidence of adverse events and the percentage of patients with dose reductions were higher with doxorubicin plus trabectedin than with doxorubicin alone. As authors comment, the favorable outcome may be a result of the efficacy of the initial chemotherapy regimen as well as the effects of subsequent treatments, including surgery, which was more feasible after combination therapy than after monotherapy; the maintenance phase of trabectedin could have contributed substantially to survival results, but the actual effect is still unknown. The longer time to disease progression with the combination therapy reinforces the potential benefits of using an effective combination therapy as early as possible in the disease course rather than waiting for sequential treatment to manage progressing sarcoma.