FDA Approves Trabectedin for Two Soft Tissue Sarcomas

Nick Mulcahy

October 23, 2015

The US Food and Drug Administration (FDA) has approved the chemotherapy trabectedin (Yondelis, Janssen Pharmaceuticals, Inc) for the treatment of two types of soft tissue sarcomas, liposarcoma and leiomyosarcoma, that are unresectable or metastatic.

This indication is limited to patients with these L-sarcomas who have previously received an anthracycline-based chemotherapy regimen.

Trabectedin improved progression-free survival (PFS) but not overall survival (OS) in its pivotal US trial. The drug is already approved for the treatment of sarcoma in Europe, Canada, and other countries.

"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, in a press statement. Trabectedin becomes a useful new addition to a limited set of treatment options, he said.

The approval is based on a pivotal phase 3 trial, which was presented this summer at the annual meeting of the American Society of Clinical Oncology, as reported by Medscape Medical News.

The study was conducted in 518 patients and showed that trabectedin provided improved efficacy compared with dacarbazine (DTIC-Dome, Bayer HealthCare Pharmaceuticals).

There was a highly statistically significant difference in PFS (4.2 months with trabectedin vs 1.5 months with dacarbazine; hazard ratio [HR] = .55; P < .0001).

Also, time to postprotocol therapy was significantly improved with the new drug (6.9 months with trabectedin vs 3.7 months with dacarbazine; HR = 0.47; P < .0001).

"Trabectedin offers a meaningful treatment option for patients with advanced liposarcoma or leiomyosarcoma," concluded the researchers, led by George D. Demetri, MD, director of the Center for Sarcoma and Bone Oncology at the Dana-Farber Cancer Institute, in Boston, Massachusetts.

However, the trial found no improvement in OS (12.4 months with trabectedin vs 12.9 months with dacarbazine).

At ASCO, the meeting's discussant of the trial, Ian Robert Judson, MD, of the Royal Marsden Cancer Hospital, London, United Kingdom, observed that the median OS in the dacarbazine group exceeded by 3 months what had been historically expected and that posttrial chemotherapy was likely a confounder.

Dr Judson noted that about 20% to 30% of patients show a prolonged clinical benefit, but that there is no biomarker to identify the likely beneficiaries.

Trabectedin's most common adverse effects in the US trial were nausea, fatigue, vomiting, diarrhea, constipation, decreased appetite, dyspnea, headache, peripheral edema, neutropenia, thrombocytopenia, anemia, elevated liver enzyme levels, and decreases in albumin level.

Trabectedin carries a warning about the risk for severe and fatal neutropenic sepsis, rhabdomyolysis, hepatotoxicity, extravasation, tissue necrosis, and heart failure.

In 2012, pazopanib (Votrient, Novartis Pharmaceuticals Corporation) was approved by the FDA for the treatment of advanced soft tissue sarcomas, which represented the first new drug option for these patients in decades.


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