Trabectedin/RT Shows Promising Responses in Resectable Retroperitoneal L-Sarcomas

Trabectedin (Yondelis) plus radiotherapy was found to be feasible and safe for patients with resectable retroperitoneal L-sarcomas, according to results from cohort C of the phase 1/2 TRASTS trial (NCT02275286) presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.

Overall response rate (ORR) was evaluated by central Choi and central RECIST criteria. The partial response rate was 29% with central Choi criteria vs 2% with central RECIST criteria; the stable disease rate was 71% vs 96%, respectively, and 17% were not evaluable by central Choi, and 2% had progressive disease via central RECIST. Of note, 96% of patients who received surgery (n = 53) experienced a complete resection.

The median relapse-free survival (RFS) rate was not reached after 37 months of follow-up (range, 28-45). The 3-year RFS rate was 76% (95% CI, 63%-89%). For those with liposarcoma, the 3-year RFS rate was 83% compared with 25% for those with leiomyosarcoma.

The median progression-free survival (PFS) was not reached, and the 3-year PFS rate was 67% (95% CI, 53%-82%). Additionally, the median overall survival (OS) was not reached, and the 3-year OS rate was 85% (95% CI, 75%-95%). The median follow-up was 40 months (95% CI, 31-48).

Regarding pathological responses, viable tumor cells, necrosis, and hyalinosis were assessed. A total of 50% or more viable tumor cells were noted in 56% of patients, 42% had between 10% and 50% viable tumor cells, and 2% had less than 10% viable tumor cells. Seventy percent of patients had necrosis vs 30% who didn’t, and 53% of patients did not have hyalinosis vs 47% who did.

“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%),” Rosa Alvarez, MD, a medical oncologist and attending physician at Hospital Universitario Gregorio Marañón, said during the presentation. “Completion of cohort D of the TRASTS study will provide further evidence of the efficacy of this approach in resectable retroperitoneal well-differentiated liposarcoma.”

The study schema for parts B, C, and D of the study included trabectedin as a 24-hour intravenous infusion on cycle 1 day 1, followed by radiotherapy at 45 Gy in 25 fractions at 1.8 Gy per cycle. Patients also received a second and third trabectedin infusion on cycle 2 day 1 and cycle 3 day 1. After a response assessment, they also received surgery. Radiotherapy began within 1 hour of trabectedin infusion completion in cycle 1. The recommended phase 2 dose for trabectedin was 1.5 mg/m².

Between February 2019 and January 2025, 56 patients were enrolled between phase 1 (n = 6) and phase 2 (n = 50). The median patient age was 61 years; 55% were male and the median tumor size was 170 mm. A total of 91% of patients had dedifferentiated liposarcoma and 9% had leiomyosarcoma, and the baseline ECOG score was 0 in 71%.

Delays to trabectedin treatment and dose reductions occurred in 32% and 16% of patients, respectively. The median number of cycles given was 3 (range, 1-3); 100% of patients were given radiotherapy and 16% experienced a radiotherapy interruption. Overall, 9 patients discontinued treatment due to toxicity; 6 were due to toxicity, 2 to patient refusal, and 1 to local progression.

Common adverse effects across both phases included lymphocytopenia (46.4%), leukopenia (33.9%), neutropenia (25.0%), and alanine aminotransferase increased (16.1%). Overall, the treatment profile was manageable and had an 84% completion rate.

The investigators also outlined several limitations of the study, including the trial being a single-arm study, the population being heterogeneous, and the sample size being limited for a meaningful subgroup analysis.

“A phase 3 study should assess efficacy compared with RT alone,” Alvarez concluded.

Reference

Alvarez RM, Hindi N, Carrasco-Garcia I, et al. Trabectedin with concomitant radiotherapy in resectable retroperitoneal L-sarcoma: A multicenter, prospective, phase I/II trial—A collaborative study by the Spanish (GEIS), Italian (ISG), and French (FSG) groups. J Clin Oncol. 2026;(suppl 16):11507. doi:10.1200/JCO.2026.44.16_suppl.11507