Doxorubicin combined with Trabectedin in systemic first-line M+/recurrent leiomyosarcoma patients

Curr Opin Oncol. 2023 Jul 1;35(4):288-291. doi: 10.1097/CCO.0000000000000961. Epub 2023 May 18.


Purpose of review: Currently, the only systemic therapy approved for advanced leiomyosarcoma is Doxorubicin-based monotherapy. Despite disappointing progression-free survival (PFS) and overall survival (OS), no combination therapy has formally ever proven to be more effective. In this clinical setting, selecting the most efficient therapy is key, as most patients become quickly symptomatic with poor performance status.This review aims to describe the current emerging role of Doxorubicin and Trabectedin in first-line setting, compared with doxorubicin alone the current standard of treatment.

Recent findings: Previous randomized trials focusing on combination therapies (Doxorubicin + ifosfamide, doxorubicin + evofosfamide, doxorubicin + Olaratumab, or Gemcitabine + Docetaxel) never reported positive results on the primary endpoint (OS or PFS). For the first time, the randomized phase III LMS-04 demonstrated that Doxorubicin and Trabectedin have a better PFS and disease control rate (DCR) compared with Doxorubicin, with higher but still manageable toxicities.

Summary: In the first-line setting, the results of this trial were pivotal for numerous reasons; Doxorubicin-Trabectedin is the first combination that has been proven to be more effective in terms of PFS, ORR and trend of OS compared with doxorubicin alone; moreover, it is clear that trials regarding soft tissue sarcoma should strive to be histology-driven.

Publication types

  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Doxorubicin
  • Humans
  • Leiomyosarcoma* / drug therapy
  • Sarcoma* / drug therapy
  • Soft Tissue Neoplasms* / drug therapy
  • Trabectedin / therapeutic use


  • Trabectedin
  • Doxorubicin