Efficacy and safety of trabectedin or dacarbazine in patients with advanced uterine leiomyosarcoma after failure of anthracycline-based chemotherapy: Subgroup analysis of a phase 3, randomized clinical trial

Gynecol Oncol. 2017 Sep;146(3):531-537. doi: 10.1016/j.ygyno.2017.06.018. Epub 2017 Jun 24.


Objective: Trabectedin demonstrated significantly improved disease control in leiomyosarcoma and liposarcoma patients in a global phase 3 trial (NCT01343277). A post hoc analysis was conducted to assess the efficacy and safety of trabectedin or dacarbazine in women with uterine leiomyosarcoma (uLMS), the largest subgroup of enrolled patients (40%).

Methods: Of 577 patients randomized 2:1 to receive trabectedin 1.5mg/m2 by 24-hour IV infusion or dacarbazine 1g/m2 by 20-120-minute IV infusion once every three weeks, 232 had uLMS (trabectedin: 144; dacarbazine: 88). The primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR: complete responses+partial responses+stable disease [SD] for at least 18weeks), duration of response (DOR), and safety.

Results: PFS for trabectedin was 4.0months compared with 1.5months for dacarbazine (hazard ratio [HR]=0.57; 95% CI 0.41-0.81; P=0.0012). OS was similar (trabectedin 13.4months vs. dacarbazine 12.9months, HR=0.89; 95% CI 0.65-1.24; P=0.51) between groups. ORR was 11% with trabectedin vs. 9% with dacarbazine (P=0.82). CBR for trabectedin was 31% vs. 18% with dacarbazine (P=0.05); median DOR was 6.5months for trabectedin vs. 4.1months for dacarbazine (P=0.32). Grade 3/4 treatment-emergent adverse events observed in ≥10% of patients in the trabectedin group included transient aminotransferase (aspartate/alanine) elevations, anemia, leukopenia, and thrombocytopenia.

Conclusions: In this post hoc subset analysis of patients with uLMS who had received prior anthracycline therapy, trabectedin treatment resulted in significantly longer PFS versus dacarbazine, with an acceptable safety profile. There was no difference in OS.

Keywords: Dacarbazine; Phase 3; Trabectedin; Uterine leiomyosarcoma.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alanine Transaminase / blood
  • Anemia / chemically induced
  • Anthracyclines / therapeutic use
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Aspartate Aminotransferases / blood
  • Dacarbazine / adverse effects
  • Dacarbazine / therapeutic use*
  • Dioxoles / adverse effects
  • Dioxoles / therapeutic use*
  • Disease-Free Survival
  • Female
  • Humans
  • Leiomyosarcoma / drug therapy*
  • Leukopenia / chemically induced
  • Middle Aged
  • Retreatment
  • Survival Rate
  • Tetrahydroisoquinolines / adverse effects
  • Tetrahydroisoquinolines / therapeutic use*
  • Thrombocytopenia / chemically induced
  • Trabectedin
  • Treatment Failure
  • Uterine Neoplasms / drug therapy*


  • Anthracyclines
  • Antineoplastic Agents, Alkylating
  • Dioxoles
  • Tetrahydroisoquinolines
  • Dacarbazine
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Trabectedin