Trabectedin (Tr) in the treatment of advanced uterine leiomyosarcomas (U-LMS): Results of a pooled analysis of five single-agent phase II studies using the recommended dose.
Tuesday 8 June 2010 .
Abstract No: 10028
Author(s): I. R. Judson, J. Blay, S. P. Chawla, J. A. Radford, A. Le Cesne, J. Verweij, M. von Mehren, J. Pontes, E. Bayever, G. D. Demetri; Cancer Research UK Centre for Cancer Therapeutics, London, United Kingdom; Université Claude Bernard Lyon I, Lyon, France; Sarcoma Oncology Center, Santa Monica, CA; University of Manchester and Christie NHS Foundation Trust, Manchester, United Kingdom; Institut Gustave Roussy, Villejuif, France; Department of Medical Oncology, Erasmus University Medical Center Daniel den Hoed Cancer Center, Rotterdam, Netherlands; Fox Chase Cancer Center, Philadelphia, PA; PharmaMar, Colmenar Viejo, Madrid, Spain; Johnson & Johnson Pharmaceutical Research and Development, Raritan, NJ; Ludwig Center, Dana-Farber Cancer Institute/Harvard Cancer Center and Sarcoma Center, Boston, MA
Abstract:
Background: Trabectedin is approved in Europe and 19 other countries around the world for second-line treatment of advanced soft tissue sarcomas (STS), with activity documented in several phase II studies. Uterine sarcoma represent 1% of all gynecological malignancies and 30% of all uterine sarcoma are U-LMS. A pooled analysis of activity and tolerability of Tr in U-LMS patients (pts) from five phase II trials is presented. Methods: Retrospective analysis was done on data from 5 different trials, with a total of 62 generally pretreated pts with advanced U-LMS (prior anthracycline-based chemotherapy: 91.9%; prior surgery: 98.4%; prior radiotherapy: 48.4%), exposed to a median of two prior chemotherapy lines (range 0-6), received iv Tr 1.5 mg/m2 24-h q3wk. Efficacy endpoints were response rate (RR) by investigator assessment (IA), progression-free survival (PFS) and overall survival (OS). Safety was also analyzed. Results: Median age 53 (range:34-75) years; median No. cycles 3 (1-38); median relative dose intensity 90%. Eleven pts achieved PR (17.7%) and 20 pts SD (32.3%; 13% ≥6 months), PD 43.5% and NE 6.5%. Median PFS was 2.5 months (95% CI:1.7-4.2); 30.7% (CI 95% 19-43) pts were progression free at 6 months. Median OS was 12.1 months, with 52% (CI 95% 39-64) and 20% (CI 95% 10-30) of pts alive at 12 and 24 months, respectively. Worst per patient grade 3-4 AEs included neutropenia (41.9%), thrombocytopenia (9.7%), anemia (9.7 %), fatigue (8.1%) and febrile neutropenia (1.6%). G-CSF was used in 17.7% of pts. Transient G3-4 ALT and AST elevations occurred in 43.5% and 30.6 % without symptoms/signs of hepatic failure. Alopecia (4.8%) and peripheral neuropathy (1.6%) were uncommon. Conclusions: Tr has activity and is reasonably safe for pts with advanced U-LMS. Nearly one-third of pts were progression-free for 6 months or more, and over half (52%) of these pretreated pts were alive at one year. RR, PFS and OS compare favorably to published outcomes with other single agents (e.g., doxorubicin). These results warrant further prospective studies in first-line U-LMS combining Tr with other active drugs.