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Trabectedin for inoperable or recurrent soft tissue sarcoma in adult patients: a retrospective cohort study
Fernando A Angarita1, Amanda J Cannell2, Albiruni R Abdul Razak3,4,5
1Division of General Surgery, Department of Surgery, University of Toronto, Toronto, ON, Canada. fernando.angarita@mail.utoronto.ca.
Background:
Trabectedin is an antineoplastic agent used for patients with soft tissue sarcoma (STS) who fail standard-of-care treatment. Real-world data of its performance is scarce. This study evaluates the safety and effectiveness of trabectedin for patients with advanced STS who were treated at a high-volume sarcoma center.
Methods:
A retrospective chart review was performed on 77 patients treated with trabectedin (24 h infusion q3w) between 01/2005 and 05/2014. Data regarding safety, objective radiological response, progression-free and overall survival were analyzed.
Results:
Median age at treatment onset was 52y [interquartile range (IQR): 45-61y]. Tumors included leiomyosarcoma (41.6%), liposarcoma (18.2%), and synovial sarcoma (13%). Trabectedin was provided as ≥ third-line chemotherapy in 71.4%. Median number of cycles was 2 (range: 1-17). Dose reduction and treatment delays occurred in 19.5 and 40.3%, respectively. Toxicities occurred in 78%, primarily for neutropenia or elevated liver enzymes. Two patients died secondary to trabectedin-induced rhabdomyolysis. Treatment was discontinued because of disease progression (84.7%), toxicity (10%), and patient preference (5%). Partial response or stable disease occurred in 14.1 and 33.8%, respectively, while 52.1% developed progressive disease. Median progression-free survival was 1.3 m (IQR: 0.7-3.5 m) and was significantly higher in patients lacking severe toxicities or progressive disease. Median overall survival was 6.7 m (IQR: 2.3-12.7 m) and was significantly higher in patients with leiomyosarcoma or liposarcoma relative to other histologies.
Conclusions:
Trabectedin has an acceptable safety profile as an anti-tumor agent. Our data further suggest there may be some benefit in using trabectedin particularly in patients with leiomyo- or liposarcoma who failed standard-of-care agents.
Insights
Trabectedin shows an acceptable safety profile for advanced soft tissue sarcoma (STS) patients. Real-world data suggests potential benefits in leiomyosarcoma or liposarcoma, especially after standard treatments fail.
Area of Science:
- Oncology
- Pharmacology
- Sarcoma Research
Background:
- Trabectedin is an antineoplastic agent for advanced soft tissue sarcoma (STS) patients who have not responded to standard treatments.
- Limited real-world data exists on trabectedin's effectiveness and safety in advanced STS.
- This study assesses trabectedin's safety and efficacy in a high-volume sarcoma center.
Purpose of the Study:
- To evaluate the real-world safety and effectiveness of trabectedin in patients with advanced soft tissue sarcoma.
- To analyze objective radiological response, progression-free survival, and overall survival in patients treated with trabectedin.
- To identify specific STS subtypes that may benefit most from trabectedin treatment.
Main Methods:
- Retrospective chart review of 77 advanced STS patients treated with trabectedin (24-hour infusion every 3 weeks) from 2005 to 2014.
- Analysis of safety data, including dose modifications, treatment delays, and toxicities (e.g., neutropenia, elevated liver enzymes, rhabdomyolysis).
- Assessment of objective radiological response, progression-free survival (PFS), and overall survival (OS).
Main Results:
- The study included patients with leiomyosarcoma (41.6%), liposarcoma (18.2%), and synovial sarcoma (13%), with 71.4% receiving trabectedin as third-line or later chemotherapy.
- Common toxicities included neutropenia and elevated liver enzymes (78% overall); two deaths were attributed to trabectedin-induced rhabdomyolysis.
- Median PFS was 1.3 months and median OS was 6.7 months; OS was significantly higher in patients with leiomyosarcoma or liposarcoma.
Conclusions:
- Trabectedin demonstrates an acceptable safety profile for advanced STS treatment.
- The findings suggest potential benefits of trabectedin in patients with leiomyosarcoma or liposarcoma who have exhausted standard treatment options.
- Further investigation into trabectedin's role in specific STS subtypes is warranted.
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