FDA Approves Trabectedin for Advanced Liposarcoma and Leiomyosarcoma

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The U.S. Food and Drug Administration has approved the novel chemotherapy drug trabectedin ­(Yondelis) for the treatment of specific soft-tissue sarcomas—liposarcoma and leiomyosarcoma—that are unresectable or metastatic. Trabectedin is a novel marine antineoplastic alkaloid with a unique mechanism of action. The active substance is a tetrahydroisoquinoline alkaloid, originally discovered in the Caribbean sea squirt, Ecteinascidia turbinata. The agent is now manufactured by total synthesis and is approved for patients who previously received chemotherapy that contained anthracycline.

“The treatment of advanced or metastatic soft-tissue sarcoma represents a difficult challenge with few effective therapeutic choices available for patients,” said Richard Pazdur, MD, Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “[This recent] approval of [trabectedin] provides a treatment option for advanced or metastatic liposarcoma and leiomyosarcoma.”

Clinical Trial Results

The effectiveness and safety of trabectedin were demonstrated in 518 clinical trial participants with metastatic or recurrent leiomyosarcoma or liposarcoma.1 Participants were randomly assigned to receive either trabectedin (n = 345) or dacarbazine (n = 173). Participants who received trabectedin experienced a 4.2-month improvement in median progression-free survival, compared to participants assigned to dacarbazine, whose disease progressed an average of 1.5 months after starting treatment.

Safety and Toxicity

The most common side effects among participants who received trabectedin were nausea, fatigue, vomiting, diarrhea, constipation, decreased appetite, dyspnea, headache, peripheral edema, neutropenia, thrombocytopenia, anemia, elevated liver enzymes, and decreases in albumin.

Trabectedin carries a warning label alerting health-care providers to the risk of neutropenic sepsis, rhabdomyolysis, hepatotoxicity, extravasation, tissue necrosis, and cardio­myopathy.   ■


1. Demetri GD, von Mehren M, Jones RL, et al: Efficacy and safety of trabectedin or dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy: Results of a phase III randomized multicenter clinical trial. J Clin Oncol. September 14, 2015 (early release online).