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WASHINGTON -- The FDA has approved trabectedin (Yondelis) for certain types of unresectable or metastatic soft-tissue sarcomas (STS) previously treated with chemotherapy.

Originally derived from a marine organism, trabectedin led to improved survival compared with chemotherapy in a randomized clinical trial, which provided the basis for FDA approval.

"The treatment of advanced or metastatic soft-tissue sarcoma represents a difficult challenge with few effective therapeutic choices available for patients," , of the FDA's Center for Drug Evaluation and Research, said in a statement. "Today's approval of Yondelis provides a treatment option for advanced or metastatic liposarcoma and leiomyosarcoma."

Initial clinical studies with trabectedin were conducted with an extract from the sea urchin Ecteinascidia turbinata. Subsequently, a synthetic version of the molecule was developed for use in later clinical trials.

Data to support the application for approval came primarily from with previously treated unresectable STS. More than 40% of the patients had received three or more prior lines of therapy, and almost 90% had received at least two prior lines of therapy.

The patients were randomized 2:1 to trabectedin or dacarbazine, each administered by intravenous infusion, and followed until disease progression or development of unacceptable toxicity. The primary endpoint was overall survival, and the key secondary endpoint was progression-free survival (PFS). Objective response rate, duration of response, time to progression, and clinical benefit rate all favored trabectedin.

At a planned interim analysis, overall survival did not differ between treatment groups (12.4 months with trabectedin and 12.9 months with dacarbazine). However, patients in the trabectedin arm had a median PFS of 4.2 months as compared with 1.5 months with dacarbazine (HR 0.55, 95% CI 0.436-0.696, P<0.0001).

The most common grade 3/4 adverse events in patients treated with trabectedin versus dacarbazine were neutropenia (40% versus 25%), thrombocytopenia (19% versus 20%), and elevated liver enzyme (ALT, 29% versus 1%). Rates of drug-related death were 2.1% versus 0%.

Yondelis is marketed by Janssen Products of Raritan, New Jersey.

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