Lenvatinib
| Evidence Level: L3 | Predicted Indications: 5 |
Table of Contents
Lenvatinib: Liposarcoma
One-Sentence Summary
Lenvatinib is an oral multi-targeted kinase inhibitor that is marketed in Australia as Lenvima. The TxGNN model predicts it may be effective for liposarcoma, with a score of 0.9951. Currently, 1 clinical trial (a single-arm Phase Ib/II study) and 4 publications relate to this prediction, giving an evidence level of L3.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Liposarcoma |
| TxGNN Prediction Score | 0.9951 |
| Evidence Level | L3 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, lenvatinib inhibits VEGFR1-3, FGFR1-4, PDGFRα, KIT and RET. These pathways drive tumour angiogenesis and growth signalling, which may also be relevant in sarcoma.
The main clinical signal comes from combining lenvatinib with eribulin, a microtubule inhibitor. The two drugs plausibly act through complementary anti-angiogenic and cytotoxic mechanisms. CDK4 amplification is common in well-differentiated and dedifferentiated liposarcoma. This provides biomarker context, but it is not a direct lenvatinib mechanism.
The evidence comes from combination use, not lenvatinib alone, and no randomised trial is available.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT03526679 | Phase 1/2 | Completed | 30 | LEADER study: single-arm trial of lenvatinib plus eribulin in inoperable or metastatic adipocytic sarcoma and leiomyosarcoma, testing safety and efficacy |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 36129471 | 2022 | Phase Ib/II single-arm trial | Clin Cancer Res | Lenvatinib plus eribulin studied for safety and efficacy in advanced liposarcoma and leiomyosarcoma (LEADER study) |
| 39103896 | 2024 | Preclinical/biomarker study | Exp Hematol Oncol | CDK4 as a prognostic biomarker in soft tissue sarcoma; CDK4 inhibition showed synergy in dedifferentiated liposarcoma |
| 29848686 | 2018 | Preclinical review | Anticancer Res | Eribulin combined with mechanistically different anticancer agents showed broad preclinical activity |
| 34326745 | 2021 | Case report | Case Rep Oncol | Tumour size reduction in dedifferentiated liposarcoma with lung metastasis under individualised treatment |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 10952K | Lenvima | Capsule 4 mg (as mesilate) | Not recorded in the data compiled |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (multi-targeted tyrosine kinase inhibitor) |
| Myelosuppression Risk | Please refer to the Product Information (PI) warnings and precautions |
| Emetogenicity Classification | Please refer to the Product Information (PI) warnings and precautions |
| Monitoring Items | Please refer to the Product Information (PI) warnings and precautions |
| Handling Protection | Please refer to the Product Information (PI) warnings and precautions |
Safety Considerations
- Drug Interactions: 100 interactions were found in the interaction screen. Those listed include:
- Major: dolasetron, cisapride
- Moderate: clarithromycin, levofloxacin, famotidine, loperamide, granisetron, palonosetron, naltrexone, and several laxatives and bowel-preparation agents (bisacodyl, picosulfuric acid, sodium sulfate, polyethylene glycol, castor oil, glycerin, lactitol, lactulose, magnesium citrate, magnesium hydroxide)
- Minor: metronidazole
Please refer to the TGA-approved Product Information (PI) for warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The only direct evidence for liposarcoma is one single-arm Phase Ib/II study of lenvatinib plus eribulin (n=30, evidence level L3), and there is no randomised trial. The data also cannot separate the contribution of lenvatinib from that of eribulin.
To proceed, the following is needed:
- Randomised or comparative data in liposarcoma that isolate lenvatinib’s contribution
- Detailed mechanism of action data
- Warnings and contraindications from the TGA-approved Product Information
- A review of the interaction profile, particularly the major interactions
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.