Overall survival and histology-specific subgroup analyses from a phase 3, randomized controlled study of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma Journal Article


Authors: Patel, S.; von Mehren, M.; Reed, D. R.; Kaiser, P.; Charlson, J.; Ryan, C. W.; Rushing, D.; Livingston, M.; Singh, A.; Seth, R.; Forscher, C.; D'Amato, G.; Chawla, S. P.; McCarthy, S.; Wang, G.; Parekh, T.; Knoblauch, R.; Hensley, M. L.; Maki, R. G.; Demetri, G. D.
Article Title: Overall survival and histology-specific subgroup analyses from a phase 3, randomized controlled study of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma
Abstract: Background: We performed a randomized phase 3 study of trabectedin versus dacarbazine in previously-treated patients with liposarcoma/leiomyosarcoma (LPS/LMS). Methods: Patients were randomized 2:1 to trabectedin (n = 384) or dacarbazine (n = 193) administered intravenously every 3 weeks. The primary objective was overall survival (OS). Secondary objectives were progression-free survival, objective response rate, safety, and patient-reported outcomes, all previously reported and demonstrating superior disease control with trabectedin. Results of the final OS analysis in preplanned subgroups of patients with LPS/LMS are presented. Results: At the time of the final OS analysis, 577 patients had been assigned randomly, including 423 (73%) with LMS and 154 (27%) with LPS. The median duration of treatment exposure was higher in the trabectedin arm compared with the dacarbazine arm (4 vs 2 cycles), as was the proportion of patients receiving an extended number of therapy courses (≥6 cycles: 42% vs 22%). This pattern was consistent across histological subgroups: the median number of treatment cycles (4 vs 2 for both subgroups) and proportion of patients with ≥6 treatment cycles (LMS, 43% vs 24%; LPS, 40% vs 16%). Despite improved disease control by trabectedin, no improvement in OS was observed; the final median OS for trabectedin versus dacarbazine was 13.7 versus 13.1 months (P =.49). Sensitivity analyses of OS suggest confounding by post-study anticancer therapies, which were utilized in most patients in both treatment arms (71% vs 69%, respectively). Conclusion: The final OS results demonstrated comparable survival between LPS/LMS patients receiving trabectedin or dacarbazine, which is consistent with the interim analysis results. Both LPS and LMS demonstrated improved disease control with trabectedin. © 2019 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society
Keywords: dacarbazine; soft tissue sarcoma; trabectedin; leiomyosarcoma; liposarcoma
Journal Title: Cancer
Volume: 125
Issue: 15
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 2019-08-01
Start Page: 2610
End Page: 2620
Language: English
DOI: 10.1002/cncr.32117
PUBMED: 31173362
PROVIDER: scopus
DOI/URL:
Notes: Source: Scopus
Altmetric Score
MSK Authors
  1. Martee L Hensley
    227 Hensley