The Royal Marsden Hospital Experience Of Trabectedin In Patients With Advanced Soft Tissue Sarcoma (Sts): Toxicity And Efficacy In A Nonselected Group

e20507 Background: Trabectedin (T) is approved in Europe for advanced soft tissue sarcoma (STS). The Royal Marsden Hospital (RMH) has treated 133 STS pts with this agent, the majority outside of clinical trial. This affords the opportunity to determine the toxicity profile and clinical benefit of T in the largest, non-selected cohort published to date. Methods: Patients who started T as a 24 hr infusion for advanced STS between May 1999 and August 2010 were analysed for clinical outcome and toxicity. Results: 133 patients were identified: 60% female; median age 50yrs (18-77yrs) and median prior treatments =1 (0-4). The histological subtypes included leiomyosarcoma (43%), myxoid liposarcoma (13%) and synovial sarcoma (12%); metastatic sites: lung (57%), liver (27%), retroperitoneal (20%). Median number of cycles was 3 (1-24); 32% ≥6 cycles, and 19% only 1 cycle (65% due to PD). Median overall PFS and OS were 67 and 153 days respectively and 28% were progression-free at 6 months. Myxoid liposarcomas were associated with significantly better PFS (median 221 vs 52 days; p=0.003), with synovial sarcomas showing a trend towards an improved PFS. Clinical benefit (PR +SD) was seen in 52% (PR=10%). Dose reductions, delays and change to q4wk schedule due to toxicity were necessary in 25%, 28% and 11% respectively. 22% required hospitalisation and 9% died within 3 weeks of therapy (3.5% toxicity-related). Overall 55% of patients experienced grade 3/4 toxicity (predominantly myelotoxicity, transaminitis, and fatigue), toxicity-related dose modification (25%), and there were 5 toxicity related deaths. Elevations in creatinine kinase occurred in 18% of cycles. Conclusions: This analysis of this largely non-selected STS cohort confirms the clinical activity of trabectedin, particularly in myxoid liposarcomas and synovial sarcomas, with approximately a third of patients experiencing prolonged disease control. Whilst it is generally well tolerated, significant toxicity was observed, with 25% of cases requiring dose reduction. Further analysis of the data is ongoing to better define those factors that may better define those not likely to benefit from T.