1422PD - Intra- and inter-patient comparison of efficacy between two phase II studies of trabectedin (T) in patients (pts) with translocation-related sarcom...

Date 27 September 2014
Event ESMO 2014
Session Sarcoma
Topics Anticancer Agents
Biological Therapy
Presenter Tsukasa Yonemoto
Citation Annals of Oncology (2014) 25 (suppl_4): iv494-iv510. 10.1093/annonc/mdu354
Authors T. Yonemoto1, S. Takahashi2, N. Araki3, H. Sugiura4, T. Ueda5, M. Takahashi6, H. Morioka7, H. Hiraga8, T. Hiruma9, T. Kunisada10, A. Matsumine11, A. Kawai12
  • 1Division Of Orthopaedic Surgery, Chiba Cancer Center, 260-8717 - Chiba/JP
  • 2Department Of Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo/JP
  • 3Dept. Of Orthopaedic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka/JP
  • 4Department Of Orthopaedic Surgery, Aichi Cancer Center Hospital, Aichi/JP
  • 5Department Of Orthopaedic Surgery, Osaka National Hospital, Osaka/JP
  • 6Division Of Orthopaedic Surgery, Shizuoka Cancer Center Hospital, Shizuoka/JP
  • 7Department Of Orthopaedic Surgery, School Of Medicine, Keio University, Tokyo/JP
  • 8Dept. Of Orthopaedic Surgery, Hokkaido Cancer Center, Hokkaido/JP
  • 9Department Of Musculoskeletal Tumor Surgery, Kanagawa Cancer Center, Kanagawa/JP
  • 10Department Of Medical Materials For Musculoskeletal Reconstruction, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama/JP
  • 11Department Of Orthopedic Surgery, Mie University Graduate School of Medicine, Mie/JP
  • 12Division Of Musculoskeletal Oncology, National Cancer Center Hospital, Tokyo/JP




T binds to the minor groove of DNA and blocks DNA repair machinery. In addition, T inhibits interactions of transcription factors with DNA. It has been reported that T is an active drug in TRS pts unresponsive to available chemotherapies with a significant increase in progression-free survival (PFS) and overall survival in study-C (ASCO 2014, Abstract: 10524). For pts with confirmed disease progression in best supportive care (BSC) arm of study-C, study-S as a rescue therapy was conducted to evaluate safety and efficacy of T. Efficacy for pts who were enrolled in both studies and efficacy difference for T between study-C and study-S were evaluated.


Target population of study-C was pts with histologically proven TRS of 14 types and unresponsive or intolerable to standard chemotherapy. After confirmation of disease progression based on image assessments in study-C, pts who were assigned to BSC were enrolled in study-S if they signed a consent form. Pts received T as a 24-hour continuous infusion every 21 days. We analyzed intra-patient comparison between BSC in study-C (BSC/C) and T in study-S (T/S), and inter-patient comparison between T in study-C (T/C) and T/S. We used a multivariate Cox proportional hazard model adjusted by background factors to estimate hazard ratios (HRs) for PFS in these comparisons.


In study-C, 76 pts were randomized: 39 in T and 37 in BSC arm. Out of 37 pts in BSC arm of study-C, 31 pts were enrolled in study-S. Number of pts for efficacy analysis of T/C, BSC/C and T/S were 37, 29 and 29 respectively. Median PFS (95% confidence interval) for T/C, BSC/C and T/S were 5.6 month (m) (4.1-7.5), 0.9 m (0.9-1.0), and 7.3 m (2.9 -9.1), respectively. HRs for PFS in intra- (BSC/C vs T/S) and inter-patient (T/C vs T/S) comparison were 0.08 (P<0.0001) and 1.03 (P=0.9390), respectively.


PFS was significantly prolonged in T/S compared with BSC/C, and was not different between T/C and T/S. Although contribution to survival is not evaluated, it is expected T could suppress progress of advanced TRS even at the late stage.


T. Ueda: I disclose that I have a consultant or advisory relationship with Daiichi-Sankyo Pharmaceutical Co.Ltd.; A. Kawai: I disclose that I have received Honoraria from TAIHO, GSK, MSD and Eisai. All other authors have declared no conflicts of interest.