Trabectedin Plus Radiotherapy Shows Promise in Retroperitoneal Sarcoma Treatment
核心洞察
The TRASTS trial demonstrated that trabectedin combined with preoperative radiotherapy achieved a 29% partial response rate by Choi criteria and 96% complete resection rates in patients with resectable retroperitoneal L-sarcomas.
At 37 months follow-up, the combination therapy showed promising survival outcomes with 3-year relapse-free survival of 76%, progression-free survival of 67%, and overall survival of 85%.
The treatment regimen was feasible and safe, with 84% of patients completing per-protocol therapy, though common grade 3/4 toxicities included neutropenia, leukopenia, and fatigue.
Trabectedin combined with preoperative radiotherapy demonstrated promising efficacy and safety in patients with resectable retroperitoneal L-sarcomas, according to results from the phase 1/2 TRASTS trial presented at the 2026 American Society of Clinical Oncology Annual Meeting.
The combination therapy achieved a partial response rate of 29% by central Choi criteria compared to just 2% by RECIST criteria, with stable disease observed in 71% and 96% of patients, respectively. Notably, 96% of the 53 patients who underwent surgery experienced complete resection.
Strong Survival Outcomes at Extended Follow-up
At a median follow-up of 40 months, survival outcomes were encouraging. The median relapse-free survival was not reached after 37 months of follow-up, with a 3-year relapse-free survival rate of 76% (95% CI, 63%-89%). Patients with liposarcoma (搜索) showed particularly favorable outcomes, achieving an 83% 3-year relapse-free survival rate compared to 25% for those with leiomyosarcoma (搜索).
The median progression-free survival was also not reached, with a 3-year progression-free survival rate of 67% (95% CI, 53%-82%). Overall survival remained robust, with the median not reached and a 3-year overall survival rate of 85% (95% CI, 75%-95%).
Treatment Protocol and Patient Characteristics
The study enrolled 56 patients between February 2019 and January 2025, including 6 in phase 1 and 50 in phase 2. The median patient age was 61 years, with 55% being male and a median tumor size of 170 mm. The majority (91%) had dedifferentiated liposarcoma (搜索), while 9% had leiomyosarcoma (搜索).
Patients received trabectedin as a 24-hour intravenous infusion at the recommended phase 2 dose of 1.5 mg/m² on cycle 1 day 1, followed by radiotherapy at 45 Gy in 25 fractions. Additional trabectedin infusions were administered on cycle 2 day 1 and cycle 3 day 1, with radiotherapy beginning within 1 hour of trabectedin infusion completion in cycle 1.
Safety Profile and Treatment Completion
The treatment regimen showed a manageable safety profile with an 84% completion rate. Common adverse effects included lymphocytopenia (46.4%), leukopenia (33.9%), neutropenia (25.0%), and increased alanine aminotransferase (16.1%). Treatment delays occurred in 32% of patients, with dose reductions needed in 16%.
Nine patients discontinued treatment due to toxicity (6 patients), patient refusal (2 patients), or local progression (1 patient). Radiotherapy interruptions occurred in 16% of patients, though 100% of patients received radiotherapy as planned.
Pathological Response Assessment
Pathological analysis revealed varying degrees of treatment response. Among evaluated patients, 56% had 50% or more viable tumor cells, 42% had between 10% and 50% viable tumor cells, and 2% had less than 10% viable tumor cells. Necrosis was observed in 70% of patients, while hyalinosis was absent in 53% of patients.
"The combination induced radiological density responses in nearly one-third of patients, with high complete resection rates (96%), promising 3-year RFS (76%), and PFS (67%)," said Rosa Alvarez, MD, a medical oncologist at Hospital Universitario Gregorio Marañón (搜索) during the presentation.
Clinical Significance and Future Directions
These results address a significant unmet need in retroperitoneal sarcoma (搜索) management, where local recurrence remains problematic even after complete surgical resection. The discrepancy between Choi and RECIST response rates highlights the importance of evaluating treatment effects beyond tumor size alone in sarcoma patients.
The investigators acknowledged several study limitations, including the single-arm design, heterogeneous patient population, and limited sample size for meaningful subgroup analysis. "A phase 3 study should assess efficacy compared with RT alone," Alvarez concluded.
Dr. Alvarez noted that "completion of cohort D of the TRASTS study will provide further evidence of the efficacy of this approach in resectable retroperitoneal well-differentiated liposarcoma (搜索)," indicating ongoing research to further validate these promising findings.