FDA Approves Trabectedin (Yondelis) for Advanced Soft-Tissue Sarcoma

The US Food and Drug Administration announced the approval of trabectedin (Yondelis) for the treatment of liposarcoma and leiomyosarcoma that is either unresectable or has metastasized. Patients must have received prior chemotherapy with an 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, the director of the FDA’s Office of Hematology and Oncology Products, in a press release.

The approval for trabectedin follows closely on the report of a randomized phase III trial in which the agent yielded better outcomes than dacarbazine in 518 patients with either liposarcoma or leiomyosarcoma. In that trial, published in September in the Journal of Clinical Oncology, all patients had unresectable, locally advanced, or metastatic disease.

The median progression-free survival (PFS) was 4.2 months with trabectedin compared with 1.5 months for dacarbazine, a benefit that was seen across all 19 subgroups analyzed. Partial responses were more common with trabectedin, though neither group had any complete responses. An interim analysis suggested overall survival may also be better, but the trial did not have enough death events to determine this conclusively.

The FDA noted that trabectedin’s new approval does carry a warning regarding the risk of neutropenic sepsis, rhabdomyolysis, hepatotoxicity, extravasation, tissue necrosis, and cardiomyopathy.

Though the large phase III trial did show a PFS benefit, a separate phase IIb trial comparing trabectedin with doxorubicin earlier this year found no difference with regard to PFS when used as first-line therapy for advanced or metastatic soft-tissue sarcoma. Results of that study were published in the European Journal of Cancer in April.

Trabectedin was first approved in Europe in 2007, and is indicated there for both soft-tissue sarcoma and for ovarian cancer. “Since Yondelis was first approved in Europe in 2007 approximately 50,000 patients in 80 countries have benefited from this therapy across all indications,” said Luis Mora, the managing director of PharmaMar, in a press release. “The approval in the United States will allow more patients with this disease to have access to a drug that will address an unmet medical need.”