Cabozantinib

證據等級: L5

預測適應症: 10 個

Cabozantinib: From Renal Cell Carcinoma to Liposarcoma

One-Sentence Summary

Cabozantinib is an oral multi-kinase inhibitor (VEGFR2 / MET / AXL) approved for renal cell carcinoma, where anti-angiogenic and MET-inhibitory activity are its core therapeutic mechanisms. The TxGNN model predicts it may be effective for Liposarcoma, with 1 clinical trial and 1 publication currently supporting this direction.

Quick Overview

Item	Content
Original Indication	Renal Cell Carcinoma
Predicted New Indication	Liposarcoma
TxGNN Prediction Score	99.83%
Evidence Level	L3
Norway Market Status	✗ Not Marketed
Number of Authorizations	0
Recommended Decision	Research Question

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available from this Evidence Pack. Based on known pharmacological information, Cabozantinib (Cabometyx®) is a small-molecule tyrosine kinase inhibitor that simultaneously suppresses VEGFR2, MET, and AXL — three kinases central to tumor angiogenesis, invasive growth, and immune evasion. Its established efficacy in renal cell carcinoma, where VEGFR/MET co-activation is the primary oncogenic driver, has been confirmed in multiple Phase 3 trials and forms the pharmacological foundation for this repurposing hypothesis.

Liposarcoma — particularly the Dedifferentiated (DDLPS) and Myxoid/Round Cell (MRCLS) subtypes — is characterised by CDK4 amplification and MDM2 amplification, while a subset of tumours also demonstrates MET overexpression and aberrant AXL signalling. Cabozantinib's MET and AXL inhibitory activity may suppress tumour cell proliferation and attenuate immune escape in these subtypes. The mechanistic link is considered moderate: although direct CDK4/MDM2 targeting is outside cabozantinib's pharmacological profile, its anti-angiogenic and MET-inhibitory components provide biologically plausible antitumour activity against the vascular and invasive characteristics common to aggressive liposarcoma subtypes.

The ongoing Phase 2 trial NCT05836571 is evaluating the combination of cabozantinib with ipilimumab and nivolumab in advanced soft tissue sarcoma — a broad category that encompasses liposarcoma as a subtype — and a Phase 1 neoadjuvant study (PMID 41770651) demonstrates that concurrent cabozantinib with radiation therapy is being actively explored in extremity sarcomas. These early signals support the biological rationale, though liposarcoma-specific efficacy data remains absent at present.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT05836571	Phase 2	Active, Not Recruiting	66	Randomised comparison of cabozantinib + ipilimumab + nivolumab versus ipilimumab + nivolumab alone in advanced soft tissue sarcoma; liposarcoma subtypes may be included but subgroup-specific results are pending — eligibility criteria should be reviewed to confirm liposarcoma representation

Literature Evidence

PMID	Year	Type	Journal	Key Findings
41770651	2026	Phase 1 RCT	American Journal of Clinical Oncology	Phase 1 safety study of neoadjuvant cabozantinib combined with concurrent radiation therapy in patients with extremity soft tissue sarcoma; primary objective was to evaluate feasibility and the risk of fistula or perforation — historically a limiting concern for this combination

Cytotoxicity

Item	Content
Cytotoxicity Classification	Targeted therapy — Multi-kinase inhibitor (VEGFR2 / MET / AXL)
Myelosuppression Risk	Moderate — neutropenia and thrombocytopenia reported in pivotal RCC trials; require close haematological monitoring
Emetogenicity Classification	Low to moderate
Monitoring Items	CBC with differential, liver function (ALT / AST / bilirubin), renal function, thyroid function, blood pressure, urine protein
Handling Protection	Please refer to the package insert warnings and precautions

Safety Considerations

Please refer to the package insert for safety information.

Conclusion and Next Steps

Decision: Research Question

Rationale: Available evidence is limited to one Phase 2 trial in broad soft tissue sarcoma (which may include liposarcoma as a subtype but has not published liposarcoma-specific efficacy outcomes) and one Phase 1 safety study; there are no liposarcoma-specific efficacy endpoints reported to date, making a formal repurposing progression decision premature.

To proceed, the following is needed:

Confirm whether NCT05836571 contains a liposarcoma-specific subgroup with independently analysable efficacy data; request sub-group results from the trial investigators if needed
Identify or conduct preclinical studies (liposarcoma cell lines, xenograft models) to establish proof-of-concept for MET/AXL-mediated activity in DDLPS or MRCLS subtypes
Obtain full MOA data via DrugBank API query to complete the mechanistic link analysis
Retrieve the package insert (Taiwan TFDA or EMA/FDA source) to complete safety profiling: warnings, contraindications, and key drug interactions
Define the most biologically relevant liposarcoma subtype(s) for prioritisation (Dedifferentiated vs. Myxoid vs. Pleomorphic) based on available MET / AXL expression data from public genomic databases (e.g., COSMIC, cBioPortal)
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.