Lenvatinib
| Evidence Level: L3 | Predicted Indications: 5 |
Table of Contents
Lenvatinib: Liposarcoma
One-Sentence Summary
Lenvatinib is an oral multi-kinase inhibitor (VEGFR1-3, FGFR1-4, PDGFRα, RET, KIT) that suppresses tumour angiogenesis. The TxGNN model predicts it may be effective for liposarcoma, with 1 clinical trial and 4 publications in the data compiled for this report, including one single-arm Phase Ib/II study (evidence level 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 |
| Canada Market Status | Marketed (marketed DINs: 8 of 8) |
| Number of DINs | 8 (marketed: 8) |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Lenvatinib blocks several receptor tyrosine kinases involved in tumour blood-vessel growth and cell proliferation, including VEGFR1-3, FGFR1-4, PDGFRα, RET and KIT. Detailed mechanism-of-action data were not otherwise available in the data compiled for this report, so this description rests on the mechanistic summary of the prediction.
In liposarcoma, standard chemotherapy gives limited benefit in advanced disease. Dedifferentiated liposarcoma is typically CDK4/MDM2-amplified, and preclinical work on eribulin combinations and CDK4 biology supports a plausible combination rationale. Anti-angiogenic kinase inhibition added to the microtubule-targeting chemotherapy eribulin offers a complementary approach.
A completed single-arm Phase Ib/II study of lenvatinib plus eribulin gives a direct clinical signal in liposarcoma and leiomyosarcoma. A case report of tumour shrinkage in dedifferentiated liposarcoma with lung metastasis adds anecdotal support. There is no randomized trial, so efficacy remains unconfirmed.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT03526679 | Phase 1/Phase 2 | Completed | 30 | Single-arm study (LEADER) 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 | Clinical Cancer Research | LEADER study of lenvatinib plus eribulin in advanced liposarcoma and leiomyosarcoma, investigating safety and efficacy |
| 39103896 | 2024 | Preclinical/biomarker study | Experimental Hematology & Oncology | CDK4 as a prognostic biomarker in soft tissue sarcoma; CDK4 inhibition shows synergy in dedifferentiated liposarcoma |
| 29848686 | 2018 | Preclinical study | Anticancer Research | Eribulin shows broad antitumour activity in combination with agents of differing mechanisms |
| 34326745 | 2021 | Case report | Case Reports in Oncology | Marked tumour shrinkage in dedifferentiated liposarcoma with lung metastasis under individualized treatment |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02450313 | LENVIMA | Not specified | Not specified |
| 02484129 | LENVIMA | Not specified | Not specified |
| 02450291 | LENVIMA | Not specified | Not specified |
| 02468239 | LENVIMA | Not specified | Not specified |
| 02484056 | LENVIMA | Not specified | Not specified |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (multi-kinase inhibitor) |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Please refer to the package insert warnings and precautions; blood counts, liver and renal function are generally monitored with antineoplastic therapy |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
- Drug Interactions: 100 interactions were found in the interaction screen. Major-level interactions include dolasetron and cisapride. Moderate-level interactions include famotidine, loperamide, bisacodyl, clarithromycin, picosulfuric acid, palonosetron, naltrexone, levofloxacin and several laxatives. Metronidazole is listed as minor.
- Lenvatinib carries pulmonary and bleeding risks. Please refer to the package insert for full warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: A completed single-arm Phase Ib/II study (NCT03526679; PMID 36129471) directly tests lenvatinib plus eribulin in advanced liposarcoma, giving a real clinical signal. There is no randomized trial, so the evidence level is L3 and the finding should be treated as hypothesis-supporting.
To proceed, the following is needed:
- A randomized or controlled study in liposarcoma to confirm efficacy
- Package insert warnings and contraindications from Health Canada
- Detailed mechanism-of-action data
- A monitoring plan for bleeding, pulmonary and cardiovascular risks and for the major drug interactions (dolasetron, cisapride)
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.