# LMS-04: doxorubicin plus trabectedin followed by trabectedin maintenance versus doxorubicin alone in metastatic leiomyosarcoma

Source: https://onco.cc/key-papers/paper-lms-04-doxorubicin-trabectedin-lancet-oncol-2022/  
OnCo record `paper-lms-04-doxorubicin-trabectedin-lancet-oncol-2022` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Combining trabectedin with doxorubicin as first-line treatment for metastatic leiomyosarcoma nearly doubled the time to progression compared with doxorubicin alone, and later showed a survival benefit, making it the first combination to beat single-agent doxorubicin in a sarcoma subtype.

## Summary

Phase 3 trial of 150 patients with metastatic or unresectable uterine or soft tissue leiomyosarcoma randomised to six cycles of doxorubicin alone or doxorubicin plus trabectedin followed by trabectedin maintenance, with surgery of residual disease allowed.

Median progression-free survival was 12.2 versus 6.2 months (hazard ratio 0.41) and response 36 versus 13 percent; the final analysis showed median overall survival of 33 versus 24 months. Grade 3 to 4 haematological toxicity was much higher with the combination.

## Fields

- Kind: Key paper
- Last checked: 2026-09-17
- Journal: The Lancet Oncology
- Year: 2022
- DOI: 10.1016/S1470-2045(22)00380-1
- Authors: Pautier P, Italiano A, Piperno-Neumann S, et al.
- Findings: Median progression-free survival 12.2 vs 6.2 months; hazard ratio 0.41.; Median overall survival 33 vs 24 months at final analysis.
- What it means: Doxorubicin-trabectedin is a first-line standard for fit patients with metastatic leiomyosarcoma, one of the few histology-specific first-line regimens in sarcoma.
- Caveats: Substantial haematological toxicity and treatment delays.; Single-country (French) trial; confirmatory data awaited.

## Sources

- Lancet Oncol 2022: https://doi.org/10.1016/S1470-2045(22)00380-1
- PubMed: https://pubmed.ncbi.nlm.nih.gov/35835135/

## Connected records

- cancers: [Leiomyosarcoma](https://onco.cc/cancers/leiomyosarcoma/), [Retroperitoneal sarcoma](https://onco.cc/cancers/retroperitoneal-sarcoma/), [Soft tissue sarcoma of the extremity (localised and advanced)](https://onco.cc/cancers/extremity-soft-tissue-sarcoma/)
- drugs: [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Trabectedin](https://onco.cc/drugs/trabectedin/)
- trials: [LMS-04](https://onco.cc/trials/lms-04/)
- journals: [The Lancet Oncology](https://onco.cc/journals/lancet-oncology/)

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