Lenvatinib
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Lenvatinib: From a Marketed Multi-Kinase Inhibitor to Liposarcoma
One-Sentence Summary
Lenvatinib is an oral multi-kinase inhibitor marketed in the US as Lenvima, and the source data does not list its original indications. The TxGNN model predicts it may be effective for liposarcoma. Support is limited: 1 completed Phase Ib/II single-arm trial (30 patients, lenvatinib plus eribulin) and 4 publications, of which only one reports on that trial.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not listed in the source data |
| Predicted New Indication | Liposarcoma |
| TxGNN Prediction Score | 99.51% |
| Evidence Level | L2 (lower edge: the Phase Ib/II study is single-arm and small, with no randomized comparator) |
| US Market Status | ✓ Marketed |
| Number of NDAs | 5 (all records under NDA206947) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Structured mechanism-of-action data is not available in the drug record. The evidence review describes lenvatinib as a multi-kinase inhibitor acting on VEGFR1-3, FGFR1-4, PDGFRα, RET and KIT. Its main action is against tumor angiogenesis, meaning the blood vessels that feed a tumor.
The tested regimen pairs lenvatinib with eribulin, a chemotherapy that blocks cell division (mitosis). The rationale is that one drug starves the tumor of blood supply while the other attacks dividing cancer cells directly.
The completed Phase Ib/II LEADER study gives a clinical signal in advanced adipocytic sarcoma (liposarcoma). It was single-arm and small (n=30), so it is not confirmatory. The other liposarcoma-related predictions (for example ovarian myxoid liposarcoma) have no entity-specific evidence. Myxoid liposarcoma also differs biologically from the dedifferentiated and well-differentiated subtypes, so extrapolation is uncertain.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT03526679 | Phase 1/2 | Completed | 30 | LEADER study: single-arm test of lenvatinib plus eribulin in inoperable or metastatic adipocytic sarcoma and leiomyosarcoma. Started July 2018 and completed October 2025. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 36129471 | 2022 | Phase Ib/II single-arm trial | Clin Cancer Res | Publication of the LEADER study (NCT03526679) on lenvatinib plus eribulin in advanced liposarcoma and leiomyosarcoma. The retrieved abstract excerpt gives no efficacy or safety figures. |
| 39103896 | 2024 | Preclinical / biomarker study | Exp Hematol Oncol | CDK4 as a prognostic biomarker in soft tissue sarcoma, with synergy from CDK4 inhibition in sequential treatment of dedifferentiated liposarcoma. Does not test lenvatinib directly. |
| 29848686 | 2018 | Preclinical study | Anticancer Res | Eribulin shows broad anticancer activity in xenograft models when combined with mechanistically different agents. Supports the combination partner, not lenvatinib itself. |
| 34326745 | 2021 | Case report | Case Rep Oncol | Reduced tumor size in a patient with dedifferentiated liposarcoma and lung metastasis after individualized targeted, surgical and chemotherapy treatment. Anecdotal. |
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| NDA206947 (5 records) | Lenvima (Eisai Inc.) | Capsule (oral) | Indication text not provided in the source data |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (multi-kinase inhibitor). The eribulin partner in the tested regimen is a conventional cytotoxic agent. |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Blood pressure, urine protein, liver function and immune-related events (from the evidence review). Add blood counts when combined with eribulin. |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
Please refer to the package insert for safety information.
The evidence review recommends monitoring for hypertension, proteinuria, hepatotoxicity and immune-related events.
Conclusion and Next Steps
Decision: Hold
Rationale: The only direct evidence is one small (n=30), single-arm Phase Ib/II study, with no randomized data in liposarcoma. Package insert warnings and contraindications are also missing, which blocks safety screening.
The strongest evidence in this pack is for renal carcinoma, with Phase 3 CLEAR RCT support (L1). That is an established, marketed use, so it validates the model rather than counting as a new repurposing finding.
To proceed, the following is needed:
- Package insert warnings and contraindications, downloaded and parsed from the FDA website (blocking gap)
- Mechanism-of-action data from DrugBank
- Efficacy and safety results of the LEADER study (PMID 36129471), and ideally a randomized or larger confirmatory study in liposarcoma
- Confirmation of lenvatinib’s labeled indications from the US NDA records
- Subtype-specific data before extending to myxoid or other rare liposarcoma variants
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.