Everolimus

證據等級: L5

預測適應症: 10 個

Everolimus: From Unspecified Original Indication to Liposarcoma

One-Sentence Summary

The evidence pack does not document Everolimus's original approved indication or mechanism of action (both flagged as data gaps), and the drug is currently not marketed in Finland. The TxGNN model predicts potential efficacy for Liposarcoma, supported by 1 clinical trial and 5 publications, though the strongest direct evidence so far comes from a combination regimen (everolimus + ribociclib) rather than everolimus monotherapy.

Quick Overview

Item	Content
Original Indication	Not documented in evidence pack (data gap)
Predicted New Indication	Liposarcoma
TxGNN Prediction Score	99.88%
Evidence Level	L2
Finland Market Status	Not Marketed
Number of Authorizations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Detailed mechanism of action data for everolimus is not available in this evidence pack (data gap DG002), and no original indication is documented. The supporting literature and trial records, however, consistently identify everolimus as an mTOR (mechanistic target of rapamycin) inhibitor — this is stated directly within the evidence pack's own repurposing rationale (e.g., for renal cell carcinoma: "Everolimus 為 mTOR 抑制劑").

The mechanistic case for liposarcoma rests on documented Akt-mTOR and MAPK pathway activation in dedifferentiated liposarcoma tumor specimens (PMID 26518767), providing a biological basis for mTOR-directed therapy in this tumor type. This is reinforced by an active Phase 2 trial (NCT03114527) combining everolimus with the CDK4/6 inhibitor ribociclib in dedifferentiated liposarcoma and leiomyosarcoma, built on preclinical evidence of synergistic growth inhibition when CDK4 and mTOR are co-inhibited (PMID 37967116).

Importantly, all current clinical evidence for this indication involves everolimus as part of a combination regimen, not as monotherapy — there is no everolimus single-agent trial or publication for liposarcoma in this evidence pack, which limits the strength of the causal link between everolimus itself and clinical benefit in this tumor type.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT03114527	Phase 2	Active, not recruiting	48	Evaluates ribociclib + everolimus combination in advanced dedifferentiated liposarcoma (Arm A) and leiomyosarcoma (Arm B) after ≥1 prior systemic therapy, assessing anti-tumor activity of the doublet; everolimus dosed at 2.5–5 mg/day alongside ribociclib 300 mg/day (3 weeks on/1 week off).

Literature Evidence

PMID	Year	Type	Journal	Key Findings
37967116	2024	RCT	Clinical Cancer Research	Reports the SAR-096 Phase 2 trial of ribociclib + everolimus in DDL/LMS; CDK4/6 and mTOR co-inhibition showed synergistic growth inhibition in preclinical tumor models, motivating the combination trial.
36003796	2022	Review	Frontiers in Oncology	Review of sarcoma patient-derived orthotopic xenograft (PDOX) models identifying effective CDK-inhibitor-based combination therapies, supporting the CDK/mTOR pathway-targeting rationale in sarcomas.
26518767	2016	Review	Tumour Biology	Demonstrates Akt-mTOR and MAPK pathway activation in dedifferentiated liposarcoma specimens (99 cases); in vitro mTOR inhibition showed antitumor effect.
29848686	2018	Review	Anticancer Research	Preclinical evaluation of eribulin combined with mechanistically distinct anticancer agents, including activity in liposarcoma models; not everolimus-specific.
41991999	2026	Review	Oncogene	Identifies XPO1 inhibitor selinexor as disrupting the core transcriptional regulatory circuitry of dedifferentiated liposarcoma; a distinct, non-mTOR therapeutic vulnerability.

Finland Market Information

Everolimus currently has no marketing authorizations on file for Finland (market status: Not Marketed, 0 licenses recorded). No product-level licensing data is available in this evidence pack.

Cytotoxicity

Item	Content
Cytotoxicity Classification	Targeted therapy (mTOR 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
Handling Protection	Please refer to the package insert warnings and precautions

Safety Considerations

Please refer to the package insert for safety information. No key warnings, contraindications, or drug-drug interaction data are available in this evidence pack (Fimea/TFDA package insert data is a blocking gap, DG001).

Conclusion and Next Steps

Decision: Hold

Rationale: The liposarcoma prediction (L2, decision stage S2) is supported by only one ongoing, non-completed combination trial and mechanistic/preclinical literature — there is no everolimus monotherapy evidence in this tumor type. Combined with a blocking gap in safety/label data (DG001), the evidence base is not yet sufficient to advance beyond a research question.

To proceed, the following is needed:

Fimea/TFDA package insert (warnings, contraindications, DDI) — required before any S1 safety pre-assessment
Confirmed original indication and mechanism of action data for everolimus (DG002)
Maturation/results of NCT03114527 (estimated completion 2025-12)
Evidence distinguishing everolimus's independent contribution from the ribociclib combination effect
Disclaimer

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