Trabectedin Fails to Improve PFS in Soft-Tissue Sarcoma

Trabectedin failed to improve progression-free survival (PFS) outcomes compared to doxorubicin as first-line therapy for advanced/metastatic soft-tissue sarcoma, according to results of a new phase IIb study.

No drug has yet shown any advantage over doxorubicin in metastatic soft-tissue sarcoma, but the efficacy of that drug is limited, with response rates ranging from 10% to 25% and a median PFS of about 6 months. The new study, led by Binh Bui-Nguyen, MD, of the Institut Bergonié in Bordeaux, France, was designed to test whether trabectedin could offer superiority over doxorubicin; results were published online ahead of print in the European Journal of Cancer.

The study’s IIb phase was designed to establish the most appropriate delivery details for the trabectedin arm-a 3-hour or 24-hour infusion schedule-as well as an efficacy analysis to determine futility. The trial was discontinued at that analysis, and a subsequent phase III portion was not conducted.

A total of 133 patients with advanced/metastatic soft-tissue sarcoma were included in the trial and were randomized to receive either doxorubicin (43 patients) or trabectedin (47 patients with 3-hour infusion schedule, 43 patients with 24-hour infusion schedule).

The median PFS was 2.8 months in the 3-hour trabectedin arm, 3.1 months in the 24-hour trabectedin arm, and 5.5 months in the doxorubicin arm. The hazard ratio (HR) for progression in the 3-hour arm vs doxorubicin was 1.50 (95% confidence interval [CI], 0.91–2.48; P = .944); the HR in the 24-hour arm vs doxorubicin was 1.13 (95% CI, 0.67–1.90; P = .675).

At the time of data cutoff, 36 patients had died-34% of the 3-hour trabectedin group, 23.3% of the 24-hour group, and 23.3% of the doxorubicin patients. Progression was the cause of death in all cases but one, which was due to toxicity. There were no significant differences in overall survival between the groups.

The one toxic death occurred in the 3-hour infusion arm. Treatment was stopped due to toxicity in 7 patients in that group (15.2%), 8 patients in the 24-hour group (19.5%), and in one doxorubicin patient (2.5%).

The authors wrote that doxorubicin remains the standard of care for first-line therapy in metastatic soft-tissue sarcoma patients, and trabectedin should remain the treatment of choice in the second-line setting. “Trabectedin 1.5 mg/m²/24-hour infusion is the overall proven approach to delivering this agent in the second-line setting for patients with advanced or metastatic soft-tissue sarcoma,” they concluded.