Presented during the Sarcoma Oral Abstract Session at the 2026 ASCO Annual Meeting, Rosa Maria Alvarez Alvarez, MD, presented phase I/II data on trabectedin with concurrent preoperative radiotherapy for patients with resectable retroperitoneal L-sarcomas.
Retroperitoneal sarcomas remain challenging, especially because local recurrence can occur even after complete surgical resection. Liposarcoma and leiomyosarcoma account for most retroperitoneal sarcomas, and dedifferentiated liposarcoma carries a particularly high risk of local failure. While preoperative radiotherapy may improve local control, the best multimodal strategy is still not clearly defined.
This study investigated whether trabectedin, an active agent in L-sarcomas with potential radiosensitizing properties, could be safely combined with preoperative radiotherapy before surgery.
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Study Design
Patients with centrally confirmed, resectable retroperitoneal L-sarcoma were enrolled. Eligible tumors included grade 2–3 dedifferentiated liposarcoma with more than 30% dedifferentiated component or grade 2–3 leiomyosarcoma.
Patients received 3 cycles of trabectedin combined with preoperative radiotherapy delivered as 45 Gy in 25 fractions.
The phase I portion used a 3+3 dose-escalation design to determine the recommended phase II dose. The phase II primary endpoint was centrally assessed Choi response. Secondary endpoints included relapse-free survival, progression-free survival, overall survival, RECIST response, pathological response, and treatment-related toxicity.
Key Findings
From February 2019 to January 2025, the study enrolled 56 patients, including 6 in phase I and 50 in phase II. The median age was 61 years, and the median tumor size was 17 cm.
Most patients had grade 2–3 dedifferentiated liposarcoma, while 5 patients had grade 2–3 leiomyosarcoma. The recommended phase II dose of trabectedin was established as 1.5 mg/m².
Per-protocol therapy was completed by 84% of patients. The most common grade 3/4 toxicities included neutropenia, leukopenia, fatigue, increased ALT, febrile neutropenia, and thrombocytopenia.
Surgery was performed in 91% of patients, and complete resection was achieved in 96% of those who underwent surgery.
By central review, Choi response showed partial response in 26.7% of patients and stable disease in 73.3%. By RECIST 1.1, partial response was uncommon, observed in 2%, while most patients had stable disease.
At a median follow-up of 40 months, the 3-year progression-free survival was 70%, and the 3-year overall survival was 85%.
Why This Matters
These results suggest that preoperative trabectedin combined with radiotherapy is a feasible and safe strategy for selected patients with resectable retroperitoneal L-sarcomas.
The study is especially relevant because it focuses on a difficult disease setting where local recurrence remains a major problem despite aggressive surgery. The discrepancy between Choi and RECIST responses also highlights the importance of looking beyond tumor size alone, particularly when evaluating treatment effects in sarcoma.
Preoperative concurrent trabectedin and radiotherapy showed acceptable safety, a meaningful density response rate, high complete resection rates, and encouraging survival outcomes in resectable retroperitoneal L-sarcomas.
These phase I/II data support further evaluation in a phase III trial comparing this regimen with radiotherapy alone.
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