Long-Term Results Of A Randomized Phase Ii Study Of Trabectedin By Two Different Dose And Schedule Regimens In Patients With Advanced Liposarcoma Or Leiomyosarcoma After Failure Of Prior Anthracyclines And Ifosfamide

10509 Background: This prospective, international randomized study evaluated two trabectedin dosing regimens [1.5 mg/m2 24-hour i.v. infusion once every 3 weeks (q3wk 24-h) vs. 0.58 mg/m2 3-hour i.v. infusion every week for 3 weeks of a 4-week cycle (qwk 3-h)] in adult patients (pts) with unresectable and/or metastatic liposarcoma or leiomyosarcoma following failure of at least prior anthracycline and ifosfamide chemotherapy. Methods: Pts were treated and continuously followed in this trial, and we now present final OS data with long-term follow-up (median = 41 mo). With 234 deaths, the study would have >80% power to detect a minimum 45% improvement in median overall survival (OS) (2-sided 5% significance level). Results: The primary efficacy endpoint (time to progression, TTP) was superior for the q3wk 24-h arm, as previously reported [Morgan, et al. J Clin Oncol: 25(18S June 20 Suppl.) 10060 (2007)]. At cutoff, 235 deaths had occurred (13% censored). This final OS analysis confirms the previously reported trend towards improved survival with trabectedin q3wk 24-h despite crossover of 32% of pts from qwk 3-h to the q3wk 24-h dosing regimen. Pts treated with q3wk 24-h had a 16% reduction in the relative risk of death (HR=0.843; p=0.1931). Median (95%CI) OS were 13.9 mo (12.5–18.6; q3wk 24-h) and 11.8 mo (9.9–14.9; qwk 3-h) (log-rank p=0.1920). OS rates at 12 mo were 60% (q3wk 24-h) and 50% (qwk 3-h). Sensitivity analyses censoring at crossover further highlighted this favorable trend in survival with trabectedin q3wk 24-h. With longer follow-up, updated median TTP (investigator assessment, 223 progression events) was 4.2 vs. 2.5 mo [HR: 0.658; p=0.0032], favoring the q3wk 24-h arm. With 59 additional cycles (for a total of 1,532 cycles) and longer exposure, trabectedin safety profile was consistent with that previously reported. Conclusions: Final survival data reinforce the internal consistency of all efficacy-related endpoints showing improved outcomes associated with the trabectedin q3wk 24-h regimen with an acceptable safety profile in this population of patients with advanced, previously-treated leiomyosarcomas and liposarcomas. [Table: see text]