Trabectedin (Tr) as single agent for advanced soft tissue sarcomas (STS) failing standard of care: Interim analysis of 1,400 patients (pts) in an expanded access program study.
Sub-category: Soft Tissue
Category: Sarcoma
Meeting: 2010 ASCO Annual Meeting
Citation: J Clin Oncol 28:7s, 2010 (suppl; abstr 10027)
Abstract No: 10027
Author(s): B. L. Samuels, W. D. Tap, S. Patel, M. von Mehren, J. T. Hamm, P. E. Kaiser, S. Schuetze, J. Li, E. Bayever, G. D. Demetri; Kootenai Cancer Center, Post Falls, ID; University of California, Los Angeles Medical Hematology Oncology, Santa Monica, CA; University of Texas M. D. Anderson Cancer Center, Houston, TX; Fox Chase Cancer Center, Philadelphia, PA; Norton Health Care, Louisville, KY; Oncology Specialists, Niles, IL; University of Michigan, Ann Arbor, MI; Johnson & Johnson Pharmaceutical Research and Development, LLC, Raritan, NJ; Johnson & Johnson Pharmaceutical Research and Development, Raritan, NJ; Ludwig Center, Dana-Farber Cancer Institute/Harvard Cancer Center and Sarcoma Center, Boston, MA
Abstract:
Background: Between 2005 and 2009, 1404 pts with advanced STS were enrolled in an Expanded Access Program (EAP) of Tr in the United States, Canada and Israel, and were treated with Tr 1.5mg/m2/ via 24h continuous IV infusion q21d. The purpose of this analysis was to assess activity and tolerability of Tr in pts treated in this EAP. Methods: A total of 25 centers participated, enrolling pts with incurable STS following failure of currently available therapies. Inclusion criteria were similar to Study ET743-STS-201 (J Clin Oncol, 2009 Sep 1;27(25):4188- 96). No restrictions were placed on the number of lines of prior therapy. Data cutoff for this analysis was September 28, 2009. Results: In this analysis of 1404 Tr-treated pts; 93% were enrolled in the US. Median age was 54 years (range16-87), 59% female; major histological subgroups were leiomyosarcoma (35%) and liposarcoma (15%). The majority of pts had prior treatment with an anthracycline and ifosfamide. Median number of Tr cycles administered was 3 (range 1-55); ≥6 cycles were given to 419 pts (30%). Median dose intensity of Tr was 1.3 mg/m2/cycle (0.20-1.77), 0.433 mg/m2/week (0.07; 0.59), relative dose intensity 87% (13-118). There were 429 (31%) dose reductions due to AE and 378 (27%) cycle delays. The most common AEs were neutropenia and transaminase elevations, however these were manageable and without serious clinical consequences. The primary reported causes of treatment termination (1191 pts) were disease progression (859 pts, 61%), adverse events (105, 7%), subject choice (99, 7%), and death (61, 4%) {fatal outcomes reported in association with adverse events 30; drug related, progressive disease 27, or other 4}. Reported best outcomes in 504 evaluable pts were CR 1 (<1%), PR 36 (7%), SD 166 (33%), PD 229 (45%). Conclusions: This EAP for heavily pretreated pts with STS represents one of the largest therapeutic experiences. Tr activity is consistent with prior trials, with a clinical benefit (objective responses + SD) of 41% with an expected toxicity profile. These results demonstrate the potential clinical utility of Tr in STS following failure of conventional therapies.