Rita De Sanctis,1 Andrea Marrari,1 Silvia Marchetti,1 Chiara Mussi,2 Luca Balzarini,3 Fabio Romano Lutman,3 Primo Daolio,4 Stefano Bastoni,4 Alexia Francesca Bertuzzi,1,5 Vittorio Quagliuolo,2 Armando Santoro1 1Department of Medical Oncology and Haematology, 2Department of Surgical Oncology, 3Department of Radiology, Humanitas Cancer Center, IRCCS, Rozzano, 4Department of Surgical Oncology, Orthopaedic Institute “G. Pini”, Milan, Italy; 5Department of Medical Oncology, Adelaide and Meath Hospital, Incorporating the National Children’s Hospital (AMNCH), Dublin, Ireland Objective: Trabectedin is effective in leiomyosarcoma and liposarcoma, especially the myxoid variant, related to the presence of the FUS-CHOP transcript. We evaluated the efficacy of trabectedin in specific subgroups of patients with soft tissue sarcomas (STS).Methods: Seventy-two patients with advanced anthracycline-pretreated STS, who received trabectedin at a dose of 1.5 mg/m2 every 3 weeks by continuous 24-hour infusion, were retrospectively analyzed. Best response rate according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria and severe adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.02) were evaluated. Secondary endpoints included progression-free survival and overall survival (OS).Results: Median age was 48 (range, 20–75) years, with a median Eastern Cooperative Oncology Group performance status of 0. The median number of previous chemotherapy regimens was 1 (range, 0–5). Median number of trabectedin cycles was 3 (range, 1–17). About 69/72 patients (95.8%) were evaluable for response: 9 patients (13%) achieved partial response and 26 (37.7%) stable disease. According to histotype, clinical benefit (partial response + stable disease) was reported in synovial sarcoma (n=5), retroperitoneal liposarcoma (n=10), myxoid liposarcoma (n=5), leiomyosarcoma (n=8), high-grade undifferentiated pleomorphic sarcoma (n=5), Ewing/peripheral primitive neuroectodermal tumor (n=1), and malignant peripheral nerve sheath tumor (n=1). Any grade AEs were noncumulative, reversible, and manageable. G3/G4 AEs included anemia (n=1, 1.4%), neutropenia (n=7, 9.6%), liver toxicity (n=6, 8.3%), and fatigue (n=2, 2.8%). With a median follow-up time of 11 (range, 2–23) months, median progression-free survival and OS of the entire cohort were 2.97 months and 16.5 months, respectively.Conclusion: Our experience confirms trabectedin as an effective therapeutic option for metastatic lipo- and leiomyosarcoma and suggests promise in synovial sarcomas and high-grade undifferentiated pleomorphic sarcoma. Keywords: trabectedin, soft tissue sarcoma, liposarcoma, leiomyosarcoma