Eribulin in Metastatic Leiomyosarcoma of Bone After Multiple Prior Lines
Eribulin is a reasonable treatment option for metastatic leiomyosarcoma of bone that has progressed on doxorubicin, gemcitabine, docetaxel, and pazopanib, though trabectedin should be prioritized as the preferred second-line agent if not yet used. 1, 2
Evidence Supporting Eribulin in Leiomyosarcoma
Regulatory Approval and Guideline Recommendations
Eribulin received EMA marketing authorization in 2016 for unresectable liposarcoma following prior anthracycline-containing therapy, based on a phase III trial comparing eribulin to dacarbazine. 1
The pivotal phase III trial (n=452) demonstrated a 2-month overall survival benefit in the combined leiomyosarcoma and liposarcoma population (13.5 vs 11.5 months; HR 0.77; p=0.017). 1, 3
ESMO-EURACAN guidelines (2018 and 2021) list eribulin as an option for previously treated leiomyosarcoma in second and further lines, with Level I, B evidence and ESMO-MCBS score of 3. 1
Activity Specifically in Leiomyosarcoma
In the phase II study, 32% of leiomyosarcoma patients (12/38 evaluable) achieved progression-free survival at 12 weeks, meeting the prespecified efficacy criteria for this histology. 1, 4
The phase III trial showed consistent benefit across both leiomyosarcoma and liposarcoma subtypes, though the survival benefit was more pronounced in liposarcoma (7 months in pleomorphic liposarcoma subtype). 1, 5
Critical Caveats for Bone Leiomyosarcoma
Extrapolation from Soft Tissue Data
Primary bone leiomyosarcoma is exceedingly rare, and all evidence derives from soft tissue leiomyosarcoma studies—treatment recommendations are extrapolated from soft tissue data. 2
The phase III trial and phase II studies enrolled patients with soft tissue sarcomas; no specific data exist for bone leiomyosarcoma. 4, 3
Preferred Alternative: Trabectedin
Trabectedin is recommended as the preferential second-line option for leiomyosarcoma by ESMO guidelines, with proven efficacy in leiomyosarcoma and liposarcoma subtypes. 1, 2
If trabectedin has not been used in your patient's treatment sequence, it should be prioritized over eribulin based on guideline recommendations. 2
Treatment Sequencing After Multiple Prior Lines
Fourth-Line Options Beyond Eribulin
Regorafenib is an option in doxorubicin-pretreated advanced non-adipogenic soft tissue sarcoma patients, even after pazopanib progression, with benefit in progression-free survival without cross-resistance concerns. 2
High-dose ifosfamide (12-14 g/m²/cycle) can circumvent tumor resistance to moderate-dose ifosfamide regimens if the patient has not received adequate high-dose exposure previously. 1, 2
Combination Strategy
- Combining trabectedin with low-dose radiation therapy is feasible and active when tumor shrinkage is crucial for symptom palliation, particularly for symptomatic bone metastases. 1, 2
Practical Considerations for Eribulin Use
Dosing and Administration
- Eribulin is administered at 1.4 mg/m² intravenously on days 1 and 8 every 21 days until disease progression or unacceptable toxicity. 4, 3
Expected Toxicity Profile
The most common grade 3-4 adverse events are neutropenia (52%), leukopenia (35%), anemia (7%), and fatigue (7%), with febrile neutropenia occurring in 6% of patients. 4
Toxicity was manageable and similar between eribulin and dacarbazine arms in the phase III trial, though grade 3 or higher adverse events were more common with eribulin (67% vs 56%). 3
Expected Efficacy
Median progression-free survival with eribulin in leiomyosarcoma patients was approximately 2.9 months in the liposarcoma subgroup analysis, though specific leiomyosarcoma-only PFS data were not separately reported. 5
Response rates are modest—the phase II study showed 32% of leiomyosarcoma patients progression-free at 12 weeks, suggesting limited but meaningful activity. 4
Local Therapy Considerations
- Oligometastatic bone disease may warrant consideration of local therapies (surgery or stereotactic radiotherapy) in addition to systemic therapy, particularly if disease-free interval was ≥1 year and limited number of lesions (3-5). 2
Clinical Trial Priority
- Enrollment in clinical trials should be strongly encouraged whenever available, as this represents the highest priority recommendation when accessible, including novel approaches such as NTRK inhibitors (entrectinib, larotrectinib) if NTRK fusions are present. 1, 2
UK Funding Limitations
- Eribulin is not currently funded in England for use in sarcomas despite EMA approval, which must be taken into account when discussing options with patients. 1