FDA Approval Summary: Trabectedin for Unresectable or Metastatic Liposarcoma or Leiomyosarcoma Following an Anthracycline-Containing Regimen

On October 23, 2015, the FDA approved trabectedin, a new molecular entity for the treatment of patients with unresectable or metastatic liposarcoma or leiomyosarcoma who received a prior anthracycline-containing regimen. Approval was based on results of a single, randomized, active-controlled, 518-p...

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Bibliographic Details
Published in:Clinical cancer research 2017-12, Vol.23 (24), p.7448-7453
Main Authors: Barone, Amy, Chi, Dow-Chung, Theoret, Marc R, Chen, Huanyu, He, Kun, Kufrin, Dubravka, Helms, Whitney S, Subramaniam, Sriram, Zhao, Hong, Patel, Anuja, Goldberg, Kirsten B, Keegan, Patricia, Pazdur, Richard
Format: Article
Language:English
Subjects:
Active control
Anaphylaxis
Anthracycline
Appetite loss
Cancer
Cardiomyopathy
Confidence intervals
Constipation
Dacarbazine
Diarrhea
Dyspnea
Edema
Extravasation
Fatigue
FDA approval
Headache
Hepatotoxicity
Intravenous administration
Liposarcoma
Metastases
Metastasis
Nausea
Neutropenia
Regulatory agencies
Respiration
Rhabdomyolysis
Side effects
Statistical analysis
Survival
Vomiting
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Summary:On October 23, 2015, the FDA approved trabectedin, a new molecular entity for the treatment of patients with unresectable or metastatic liposarcoma or leiomyosarcoma who received a prior anthracycline-containing regimen. Approval was based on results of a single, randomized, active-controlled, 518-patient, multicenter study comparing the safety and efficacy of trabectedin 1.5 mg/m as a 24-hour continuous intravenous (i.v.) infusion once every 3 weeks with dacarbazine 1,000 mg/m i.v. once every 3 weeks. Treatment with trabectedin resulted in a statistically significant improvement in progression-free survival (PFS), with a PFS of 4.2 months and 1.5 months for trabectedin and dacarbazine, respectively (HR, 0.55; 95% confidence interval, 0.44-0.70; unstratified log-rank test, < 0.001). The most common adverse reactions (≥20%) were nausea, fatigue, vomiting, constipation, decreased appetite, diarrhea, peripheral edema, dyspnea, and headache. Serious adverse reactions included anaphylaxis, neutropenic sepsis, rhabdomyolysis, hepatotoxicity, cardiomyopathy, and extravasation resulting in tissue necrosis. A postmarketing trial was required to evaluate the serious risk of cardiomyopathy. This approval provides another treatment option in a setting where no drug has been shown to improve overall survival. A key regulatory consideration during review of this application was the use of PFS as an endpoint to support regular approval of trabectedin. .
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.ccr-17-0898