Trabectedin in soft tissue sarcomas

Area of Science:

• Pharmacology
• Oncology
• Marine Biotechnology

Background:

• Trabectedin (Yondelis®) is a synthetic anticancer agent derived from Ecteinascidia turbinata.
• It is approved globally for treating soft tissue sarcoma (STS).
• Trabectedin functions as an isoquinoline alkylating agent with unique DNA minor groove binding.

Purpose of the Study:

• To evaluate the efficacy and safety of trabectedin in patients with liposarcoma or leiomyosarcoma.
• To compare two different administration schedules for trabectedin: a 24-hour infusion every 3 weeks versus a weekly regimen.
• To assess the impact of trabectedin on disease progression and overall survival in STS patients.

Main Methods:

• A Phase II clinical trial (STS-201) involving 270 patients with liposarcoma or leiomyosarcoma.
• Patients were randomized to receive either trabectedin 1.5 mg/m² as a 24-hour intravenous (IV) infusion every 3 weeks or as a weekly regimen (0.58 mg/m²; 3-hour IV infusion for three consecutive weeks in a 4-week cycle).
• The primary endpoint was the risk of disease progression.

Main Results:

• Trabectedin administered as a 24-hour infusion every 3 weeks resulted in a statistically significant and clinically relevant 27% reduction in the risk of disease progression (p = 0.0302).
• The 12-month overall survival rate was 60% in the group receiving the 24-hour infusion every 3 weeks.
• Trabectedin was generally well tolerated, with the most frequent severe adverse events being neutropenia and elevated transaminases (47% each).

Conclusions:

• The 24-hour intravenous infusion of trabectedin every 3 weeks is an effective regimen for patients with liposarcoma or leiomyosarcoma.
• The drug demonstrated a favorable safety profile with no cumulative toxicities observed, even with long-term exposure.
• Trabectedin's multitarget mechanisms, including effects on the tumor microenvironment, contribute to its efficacy in treating soft tissue sarcoma.