Trabectedin plus doxorubicin can prolong progression-free survival (PFS), when compared with doxorubicin alone, in patients with advanced leiomyosarcoma, according to a phase 3 trial published in The Lancet Oncology

Adding trabectedin to doxorubicin doubled the median PFS, improved the objective response rate, and prolonged the duration of response in this trial. 

The phase 3 LMS-04 trial ( Identifier: NCT02997358) included 150 patients with metastatic or relapsed unresectable leiomyosarcoma not previously treated with chemotherapy. 

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In the overall cohort, the median age at baseline was 61 years, and 90% of patients had metastatic disease (n=131). Most patients (n=83) had soft tissue leiomyosarcoma, but 67 had uterine leiomyosarcoma. 

Patients were randomly assigned to receive doxorubicin alone (n=76) or in combination with trabectedin (n=74). In the monotherapy arm, patients received doxorubicin at 75 mg/m² once every 3 weeks for up to 6 cycles. In the combination arm, patients received doxorubicin at 60 mg/m² plus trabectedin at 1.1 mg/m² once every 3 weeks for up to 6 cycles, followed by maintenance with trabectedin alone. 

Patients could undergo surgery after 6 cycles of treatment. There were 15 patients in the combination arm and 6 in the monotherapy arm who had surgery.

The primary endpoint was PFS. The median PFS was significantly longer with trabectedin-doxorubicin than with doxorubicin alone — 12.2 months and 6.2 months, respectively (adjusted hazard ratio [aHR], 0.41; 95% CI, 0.29-0.58; P <.0001). 

The 12-month PFS rate was 50.7% in the combination arm and 16.0% in the monotherapy arm. This 24-month PFS rate was 30.2% and 5.3%, respectively.

The objective response rate was 36% with trabectedin-doxorubicin and 13% with doxorubicin alone. The disease control rate was 91.9% and 78.9%, respectively.

The median duration of response was 12.7 months with trabectedin-doxorubicin and 5.6 months with doxorubicin alone (HR, 0.36; 95% CI, 0.17-0.77; P =.009).

Adverse events occurred more frequently in the trabectedin arm. The rate of grade 3-4 AEs was 96% in the trabectedin-doxorubicin arm and 52% in the doxorubicin arm. 

The most common grade 3-4 events (in the combination and monotherapy arms, respectively) were neutropenia (80% vs 13%), febrile neutropenia (28% vs 9%), anemia (31% vs 5%), and thrombocytopenia (47% vs 0%). 

There was 1 treatment-related death in the doxorubicin-alone arm (due to cardiac failure). There were none in the combination arm.

“Doxorubicin plus trabectedin in first-line therapy was found to significantly increase progression-free survival in patients with metastatic or unresectable leiomyosarcomas compared with doxorubicin alone, despite higher but manageable toxicity, and could be considered an option for the first-line treatment of metastatic leiomyosarcoma,” the researchers concluded. 

Disclosures: This study was supported by PharmaMar. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Pautier P, Italiano A, Piperno-Neumann S, et al. Doxorubicin alone versus doxorubicin with trabectedin followed by trabectedin alone as first-line therapy for metastatic or unresectable leiomyosarcoma (LMS-04): A randomised, multicentre, open-label phase 3 trial. Lancet Oncol. Published online July 11, 2022. doi:10.1016/S1470-2045(22)00380-1

This article originally appeared on Cancer Therapy Advisor