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

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

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Free PMC article
Clinical Trial

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

Martee L Hensley et al. Gynecol Oncol. .
Free PMC article

Abstract

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.

Conflict of interest statement

CONFLICT OF INTEREST STATEMENTS

Martee L. Hensley: grants from Janssen during the conduct of the study; personal fees from Janssen, Lilly, EMD Serono, Tesaro, OncLive, and UpToDate outside the submitted work; spouse is an employee of Sanofi.

Shreyaskumar R. Patel: grants and personal fees from Janssen, Eisai, and Morphotek; personal fees from EMD-Serono, CytRx, Bayer, Eli Lilly, Epizyme, and Novartis outside the submitted work.

Margaret von Mehren: personal fees from Janssen and Eisai outside the submitted work.

Kristen Ganjoo: Janssen advisory board outside the submitted work.

Robin L. Jones: has worked as a consultant for PharmaMar.

Daniel Rushing: personal fees from Eisai Pharmaceutical, Bayer Pharmaceutical, and Lilly Pharmaceutical outside the submitted work.

Arthur Staddon and Mohammed Milhem: nothing to disclose.

Bradley Monk: St Joseph’s Hospital institution has received research grants from Novartis, Amgen, Lilly, Genentech, Janssen/Johnson & Johnson, Array, TESARO, and Morphotek; he has received honoraria for speaker bureaus from Roche/Genentech, AstraZeneca, Janssen/Johnson & Johnson, Myriad, TESARO, and Clovis; he has been a consultant for Roche/Genentech, Merck, TESARO, AstraZeneca, Gradalis, Advaxis, Cerulean, Amgen, Vemillion, ImmunoGen, Pfizer, Bayer, NuCana, Insys, GlaxoSmithKline, Verastem, Mateon, PPD, Clovis, Precision Oncology, Biodesix, Perthera, ImmunoGen, and Cue.

George Wang, Sharon McCarthy, Roland E. Knoblauch, and Trilok V. Parekh: each is an employee with stock options at Janssen Research & Development, LLC.

Robert G. Maki: personal fees (consulting) and previously received support to conduct clinical trials at his institution from Janssen/PharmaMar.

George D. Demetri: personal fees and non-financial support from Janssen Oncology.

Figures

FIGURE 1
FIGURE 1
Patient disposition: uLMS subset.
FIGURE 2
FIGURE 2
Kaplan-Meier estimates for (A) OS and (B) PFS in the trabectedin and dacarbazine groups: uLMS subset.
FIGURE 2
FIGURE 2
Kaplan-Meier estimates for (A) OS and (B) PFS in the trabectedin and dacarbazine groups: uLMS subset.

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