A randomized phase II study comparing trabectedin (T) and best supportive care (BSC) in patients (pts) with translocation-related sarcomas (TRS).

Session Type and Session Title: 
Poster Highlights Session, Sarcoma
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 10524)
Shunji Takahashi, Nobuhito Araki, Hideshi Sugiura, Takafumi Ueda, Mitsuru Takahashi, Hideo Morioka, Tsukasa Yonemoto, Hiroaki Hiraga, Toru Hiruma, Toshiyuki Kunisada, Akihiko Matsumine, Akira Kawai; Department of Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan; Department of Orthopaedic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan; Department of Orthopedic Surgery, Aichi Cancer Center Hospital, Aichi, Japan; Department of Orthopaedic Surgery, Osaka National Hospital, Osaka, Japan; Division of Orthopaedic Surgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan; Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo, Japan; Division of Orthopaedic Surgery, Chiba Cancer Center, Chiba, Japan; Department of Orthopaedic Surgery, Hokkaido Cancer Center, Sapporo, Japan; Department of Musculoskeletal tumor surgery, Kanagawa Cancer Center, Kanagawa, Japan; Department of Medical Materials for Musculoskeletal Reconstruction,Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan; Department of Orthopedic Surgery, Mie University Graduate School of Medicine, Mie, Japan; Division of Musculoskeletal Oncology, National Cancer Center Hospital, Tokyo, Japan

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Abstract Disclosures


Background: T binds to the minor groove of DNA and blocks DNA repair machinery following the inhibition of cell cycle and proliferation. In addition, T inhibits interactions of transcription factors including TRS-related transcription factors with the DNA in a competitive manner. This is the first time that the progression-free survival (PFS) of T is compared with BSC as a second or later line treatment in pts with TRS in a multi-center, open, phase II trial. Methods: Main inclusion criteria were the following: histologically proven TRS; unresponsiveness or intolerability to standard chemotherapy regimens (pts with extraskeletal Ewing sarcoma (EES), myxoid liposarcoma (ML), or synovial sarcoma (SS) should have received anthracyclines); at least 1 measurable baseline lesion (RECIST v1.1); confirmed disease progression (per RECIST) compared with the image assessment performed during the previous 6 months(m). Pts stratified by subtype (alveolar rhabdomyosarcoma, ESS, ML, SS vs other TRS) were randomly assigned 1:1 to T (1.2 mg/m2 in 24h continuous infusion every 21 days) or BSC. The primary endpoint was PFS by independent review assessment (IR). This study had 80% power for a one-sided 5% significance level test given a hazard ratio (HR) (T relative to BSC) of 0.50. Sample size goal was 74 pts with an event goal of 52 events by IR requiring a total of 60 events by investigator’s assessment (IA). PFS and overall survival (OS) were analyzed using a stratified log-rank test. Results: Data cut-off date was 8th February 2014. Total of 76 pts were enrolled. Number of pts for efficacy analysis was 73 (T: 37 pts and BSC: 36 pts). Median PFS (90% confidence interval(CI))for T and BSC were 5.6 m (4.2-7.5) and 0.9 m (0.9-1.0), respectively (p<0.0001; HR=0.07, 90% CI: 0.03-0.14). Median OS (95% CI) for T and BSC were not reached (NR) (12.8-NR) and 8.0 m (7.0-NR), respectively (p=0.025; HR=0.38, 95% CI: 0.16-0.91) under permission of crossover. Conclusions: T is an active drug in TRS pts pretreated by available chemotherapies with a significant increase in PFS and OS. Clinical trial information: JapicCTI-121850.