FDA Approves Trabectedin for Liposarcoma, Leiomyosarcoma

Treatment shows significant improvement in progression-free survival in patients with unresectable or metastatic liposarcoma or leiomyosarcoma.

The FDA last week approved trabectedin (Yondelis Injection) for the treatment of patients with unresectable or metastatic liposarcoma or leiomyosarcoma who have previously received anthracycline-containing therapy.

The approval comes following a multicenter, randomized, open-label, active-controlled trial.

During the study, patients received trabectedin as an intravenous infusion over 24 hours once every 3 weeks, or they received dacarbazine as an intravenous infusion over 20 to 120 minutes once every 3 weeks.

The efficacy outcome measures taken into consideration were investigator-assessed progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST v1.1), overall survival, confirmed objective response rate, and response duration.

Patients randomized to the dacarbazine group were not administered trabectedin at the time of disease progression.

The study results showed a significant improvement in PFS. Those in the trabectedin arm had a median PFS of 4.2 months, and those in the dacarbazine arm had a median PFS of 1.5 months.

However, there was no difference between the two arms in overall survival. The confirmed objective response rates were 7% and 6% on the trabectedin and dacarbazine arms, respectively.

Adverse events observed in trabectedin are neutropenic sepsis, rhabdomyolysis, cardiomyopathy, hepatotoxicity, anaphylaxis, and extravasation leading to tissue necrosis.

Of the 378 patients who received at least one dose of trabectedin in the randomized trial, the most common side effects were nausea, fatigue, vomiting, constipation, decreased appetite, diarrhea, peripheral edema, dyspnea, and headache.

The most common treatment-emergent, grade 3 or 4 laboratory abnormalities were neutropenia, increased ALT, thrombocytopenia, anemia, increased AST, and increased creatine phosphokinase.

Trabectedin is recommended at a rate of 1.5 mg/m² as a 24-hour intravenous infusion through a central venous line every 3 weeks in patients with normal bilirubin and with AST and ALT less than or equal to 2.5 times the upper limit of normal.

It is recommended that the treatment be pre-medicated with dexamethasone 20 mg intravenously 30 minutes prior to each dose of trabectedin. There is not currently a recommended dose of trabectedin for patients with serum bilirubin levels above the institutional upper limit of normal.