LMS04: Doxorubicin-Trabectedin with Trabectedin Maintenance in Leiomyosarcoma
Published in: New England Journal of Medicine
Authors: Pautier P et al.
Publication Year: 2024
Source: N Engl J Med 2024; 391:789-799
Objective of the Study:
This trial, LMS04, aimed to refine the treatment strategy for patients with metastatic leiomyosarcoma (LMS), specifically targeting the uterine and soft tissue subtypes. The goal was to evaluate the efficacy of a combination treatment approach using Doxorubicin and Trabectedin followed by Trabectedin maintenance, and to assess whether this could serve as a superior first-line therapeutic option for these patients.
Study Design:
- Type: Randomized Phase III Multicenter Trial
- Patients Enrolled: 150
- Inclusion Criteria:
- Age ≥ 18 years
- Confirmed metastatic or unresectable leiomyosarcoma
- No prior chemotherapy
- Presence of at least one measurable lesion based on RECIST 1.1 criteria
- Adequate liver, hematologic, and cardiac functions
- Use of effective contraception for both genders
Treatment Groups:
- Doxorubicin-Trabectedin Group (n = 74): Patients received an induction treatment of Doxorubicin and Trabectedin, followed by Trabectedin maintenance therapy.
- Doxorubicin Group (n = 76): Patients received Doxorubicin alone.
Primary Outcome:
- Progression-Free Survival (PFS):
- Doxorubicin-Trabectedin group: 12 months
- Doxorubicin group: 6 months
- Hazard Ratio (HR) for progression or death: 0.37 (95% CI: 0.26–0.53)
Secondary Outcomes:
- Median Overall Survival (OS):
- Doxorubicin-Trabectedin group: 33 months
- Doxorubicin group: 24 months
- Adjusted HR for death: 0.65 (95% CI: 0.44–0.95)
- Grade 3 or 4 Adverse Events:
- Doxorubicin-Trabectedin group: 97%
- Doxorubicin group: 56%
- P-value: < 0.001
Conclusion:
The combination therapy of Doxorubicin and Trabectedin, followed by Trabectedin maintenance, resulted in significantly improved progression-free survival and overall survival compared to Doxorubicin alone. Despite the higher rate of Grade 3 or 4 adverse events in the combination group, the survival benefits make this an effective first-line treatment option for patients with metastatic or unresectable uterine or soft-tissue leiomyosarcoma.
Implications for Clinical Practice:
This trial highlights a promising treatment strategy for leiomyosarcoma, suggesting that the addition of Trabectedin can extend survival and delay disease progression in this challenging cancer subtype. As with any treatment that comes with increased adverse events, careful patient selection and management of side effects are critical.
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