FDA Approval Summary: Trabectedin for Unresectable or Metastatic Liposarcoma or Leiomyosarcoma Following an
Amy Barone1, Dow-Chung Chi2, Marc R Theoret2
1Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland. amy.barone@fda.hhs.gov.
Abstract:
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/m2 as a 24-hour continuous intravenous (i.v.) infusion once every 3 weeks with dacarbazine 1,000 mg/m2 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, P < 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. Clin Cancer Res; 23(24); 7448-53. ©2017 AACR.
Insights
Trabectedin significantly improved progression-free survival for patients with advanced liposarcoma or leiomyosarcoma compared to dacarbazine. This FDA-approved drug offers a new treatment option for these rare cancers.
Area of Science:
- Oncology
- Pharmacology
Background:
- Trabectedin is a novel molecular entity approved by the FDA for treating unresectable or metastatic liposarcoma and leiomyosarcoma.
- Patients must have previously received an anthracycline-containing regimen before being eligible for trabectedin treatment.
Purpose of the Study:
- To compare the efficacy and safety of trabectedin versus dacarbazine in patients with advanced liposarcoma or leiomyosarcoma.
- To evaluate trabectedin as a new treatment option in a setting with limited therapeutic choices.
Main Methods:
- A randomized, active-controlled, multicenter study involving 518 patients.
- Patients received either trabectedin (1.5 mg/m2 IV infusion every 3 weeks) or dacarbazine (1,000 mg/m2 IV every 3 weeks).
- Progression-free survival (PFS) was the primary efficacy endpoint.
Main Results:
- Trabectedin demonstrated a statistically significant improvement in PFS (4.2 months) compared to dacarbazine (1.5 months).
- The hazard ratio for PFS was 0.55 (95% CI, 0.44-0.70; P < 0.001).
- Common adverse reactions included nausea, fatigue, and vomiting; serious risks involved cardiomyopathy and neutropenic sepsis.
Conclusions:
- Trabectedin offers a significant survival benefit for patients with advanced liposarcoma or leiomyosarcoma previously treated with anthracyclines.
- The study's reliance on PFS as a primary endpoint for regular FDA approval was a key regulatory consideration.
- This approval expands treatment options for patients with these rare soft tissue sarcomas.
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