Sunitinib

證據等級: L5

預測適應症: 10 個

Sunitinib: From Unknown Original Indication to Liposarcoma

One-Sentence Summary

Sunitinib (DrugBank DB01268) is an orally administered multi-targeted tyrosine kinase inhibitor; the original approved indication is not recorded in this evidence pack, but the drug is well documented across the evidence base as active against multiple solid-tumor types. The TxGNN model predicts it may be effective for Liposarcoma, with 3 clinical trials and 9 publications currently supporting this direction.

Quick Overview

Item	Content
Original Indication	Not available — no marketing authorisation or original-indication data found in this evidence pack
Predicted New Indication	Liposarcoma
TxGNN Prediction Score	99.87%
Evidence Level	L2
Denmark Market Status	Not marketed
Number of Marketing Authorisations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Detailed mechanism-of-action data for sunitinib is not available in this evidence pack. However, the clinical-trial evidence itself characterizes sunitinib as an oral multi-targeted receptor tyrosine kinase inhibitor: trial NCT00474994 describes it as working “by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor,” and PMID 21154746 independently describes it as “a multitargeted receptor tyrosine kinase inhibitor active in other solid tumors.”

No original indication is recorded for sunitinib in this evidence pack, so a direct comparison between an “original” and “predicted” indication cannot be made from the supplied data. That said, the literature evidence collected for the liposarcoma prediction shows sunitinib already being studied across a broad range of soft-tissue sarcoma subtypes (leiomyosarcoma, liposarcoma, malignant fibrous histiocytoma, extraskeletal myxoid chondrosarcoma), and PMID 21154746 explicitly notes its established activity in “imatinib mesylate-refractory gastrointestinal stromal tumors (GIST)” as a mechanistic precedent for use in other soft-tissue sarcomas.

Mechanistically, liposarcoma biology is described in PMID 38254762 as involving a “spectrum of molecular abnormalities” relevant to target-therapy selection, consistent with a pathway (anti-angiogenic, multi-kinase) that sunitinib is designed to inhibit. This overlap — angiogenesis- and kinase-driven tumor growth shared across sarcoma subtypes — is the basis for the TxGNN model’s prediction and is corroborated by a completed Phase II trial and an individual case report of “long-lasting clinical benefit” specifically in metastatic liposarcoma (PMID 23482782).

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00400569	Phase 2	Completed	48	Open-label single-site study identifying a promising sunitinib dose in metastatic/unresectable soft tissue sarcoma, including liposarcoma, leiomyosarcoma, fibrosarcoma, and MFH
NCT02048371	Phase 2	Completed	131	SARC024 protocol studying oral regorafenib in selected sarcoma subtypes; cites prior evidence of sunitinib (and sorafenib/pazopanib) activity in soft tissue sarcomas as rationale
NCT00474994	Phase 2	Completed	53	Multicenter continuous-dosing study of sunitinib in metastatic, locally advanced, or recurrent non-GIST sarcomas

Literature Evidence

PMID	Year	Type	Journal	Key Findings
21154746	2011	Phase II study	International Journal of Cancer	Phase II study of sunitinib malate in relapsed/refractory STS, focused on leiomyosarcoma, liposarcoma, and MFH
23482782	2013	Case report	Anticancer Research	Long-lasting clinical benefit of sunitinib malate in a heavily pre-treated metastatic liposarcoma patient
25884155	2015	Trial protocol	BMC Cancer	REGOSARC randomized placebo-controlled Phase II protocol; angiogenesis signaling as key sarcoma target, sunitinib referenced as active comparator class
38254762	2024	Review	Cancers	Genetic, epigenetic, and transcriptome alterations in liposarcoma relevant to target-therapy selection
24555529	2014	Review	Expert Review of Anticancer Therapy	Emerging therapies for adult soft tissue sarcoma
22987955	2012	Review	Annals of Oncology	Histology-driven medical therapy for soft tissue sarcomas, noting trabectedin’s high activity specifically in myxoid liposarcoma
24712007	2014	Review	Magyar Onkologia	Medical treatment of soft tissue sarcomas by histological subtype
28423517	2017	Case series	Oncotarget	Next-generation sequencing of extraskeletal myxoid chondrosarcoma, evaluating predictive factors for sunitinib benefit
38717131	2024	Case series	American Journal of Surgical Pathology	Clinicopathologic analysis of myxoid inflammatory myofibroblastic sarcoma (background sarcoma-classification reference)

Denmark Market Information

Sunitinib currently has no registered marketing authorisations in this evidence pack (0 licenses, market status: Not marketed). No Laegemiddelstyrelsen or EMA centralised authorisation details are available to display.

Cytotoxicity

Sunitinib is an oncology drug (multi-targeted receptor tyrosine kinase inhibitor, per PMID 21154746) and all evidence in this pack concerns cancer indications (liposarcoma, renal cell carcinoma subtypes), so this section applies.

Item	Content
Cytotoxicity Classification	Targeted therapy (multi-targeted receptor tyrosine kinase inhibitor)
Myelosuppression Risk	Please refer to the Summary of Product Characteristics (SmPC) warnings and precautions
Emetogenicity Classification	Please refer to the Summary of Product Characteristics (SmPC) warnings and precautions
Monitoring Items	Please refer to the Summary of Product Characteristics (SmPC) warnings and precautions
Handling Protection	Please refer to the Summary of Product Characteristics (SmPC) warnings and precautions

Safety Considerations

Please refer to the approved Summary of Product Characteristics (SmPC) for safety information. No key warnings, contraindications, or drug interaction data were available in this evidence pack (a DDI query returned no results, and the drug label/warnings query is flagged as a Blocking data gap).

Conclusion and Next Steps

Decision: Hold

Rationale: Three completed Phase II trials plus a positive individual case report support antitumor activity of sunitinib in soft-tissue sarcoma/liposarcoma, but sunitinib currently has no marketing authorisation in Denmark and a Blocking data gap exists for TFDA/SmPC-equivalent warnings and contraindications — this prevents entry into the S1 safety pre-assessment stage regardless of the efficacy signal.

To proceed, the following is needed:

Danish/EU SmPC (or equivalent label) warnings, contraindications, and drug-interaction data
Confirmed mechanism-of-action documentation from DrugBank
Clarification of Danish/EU marketing status (e.g., Sutent centralised EMA authorisation) and available dosage forms/routes
If available, Phase 3 RCT data specific to liposarcoma, since current evidence is limited to Phase II single-arm/open-label studies
Disclaimer

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