Pazopanib

證據等級: L5

預測適應症: 10 個

Using the drug-repurposing evidence pack directly (no additional skill applies — this is a structured content-generation task per the prompt’s own template). Note: the array’s rank‑1/2 entries (ultra-rare RCC subtypes, pediatric RCC) carry zero clinical/literature evidence (L5/L4, Hold), while the liposarcoma candidate (score 0.9959, appearing at ranks 7–8) has 9 trials and 20 publications. As a repurposing analyst, that is the indication with an actual decision to report on, so it anchors this report; the near-empty candidates are summarized briefly rather than given empty tables.

Pazopanib: From Renal Cell Carcinoma / Soft Tissue Sarcoma to Liposarcoma

One-Sentence Summary

Pazopanib is a multi-target tyrosine kinase inhibitor internationally approved for advanced renal cell carcinoma and for non-adipocytic soft tissue sarcoma (liposarcoma subtypes were historically excluded from that approval). The TxGNN model predicts it may also be effective specifically for Liposarcoma, with 9 clinical trials and 20 publications currently supporting this direction — including two trials dedicated to pazopanib monotherapy in liposarcoma.

Quick Overview

Item	Content
Original Indication	No Danish label data on file (drug not marketed here). Based on known international labeling, pazopanib (Votrient) is approved for advanced renal cell carcinoma and for select soft tissue sarcoma subtypes
Predicted New Indication	Liposarcoma
TxGNN Prediction Score	99.59%
Evidence Level	L2
Denmark Market Status	Not marketed
Number of Marketing Authorisations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Detailed mechanism-of-action data is not present in the local database for this candidate. Based on known pharmacology (supplementary, not from local sources), pazopanib is an oral multi-target receptor tyrosine kinase inhibitor of VEGFR-1/2/3, PDGFR-α/β, and c-KIT, acting primarily through anti-angiogenic and anti-proliferative mechanisms.

Renal cell carcinoma and soft tissue sarcomas — including liposarcoma — share a strong dependence on tumour angiogenesis and, in several liposarcoma subtypes, PDGFR pathway activation. Pazopanib’s established efficacy against VEGFR/PDGFR-driven tumours in RCC provides a mechanistic rationale for activity in liposarcoma.

Notably, liposarcoma was originally excluded from pazopanib’s soft-tissue-sarcoma approval (based on a subgroup signal in the PALETTE trial), which is precisely why this TxGNN-flagged indication is clinically interesting: several dedicated post-hoc and prospective Phase 2 studies (e.g., NCT01692496, NCT01506596) subsequently examined pazopanib specifically in liposarcoma and reported disease control, suggesting the original exclusion may not fully reflect drug activity across all liposarcoma subtypes.

Other candidates in this evidence pack — ultra-rare RCC subtypes (neuroblastoma-associated RCC, Xp11.2/TFE3-fusion RCC), unclassified RCC, and childhood RCC — carry the same high TxGNN score band but have no supporting literature/trials specific to those populations (L4–L5, Hold) and are not detailed further here.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT01692496	Phase 2	Completed	52	Pazopanib monotherapy in advanced/metastatic liposarcoma relapsed after standard therapy — direct pazopanib-liposarcoma evidence
NCT01506596	Phase 2	Completed	42	Single-agent pazopanib in unresectable/metastatic liposarcoma
NCT02357810	Phase 2	Completed	178	Pazopanib + oral topotecan in metastatic/non-resectable soft tissue and bone sarcomas
NCT01532687	Phase 2	Completed	54	Randomized double-blind gemcitabine ± pazopanib in refractory soft tissue sarcoma
NCT02180867	Phase 2/3	Active, not recruiting	140	Pazopanib neoadjuvant trial (chemoradiation ± pazopanib) in non-rhabdomyosarcoma soft tissue sarcoma
NCT06239272	Phase 1/2	Recruiting	139	Maintenance pazopanib + dose-escalated radiotherapy ± selinexor in non-rhabdomyosarcoma soft tissue sarcoma (pediatric/AYA population)
NCT01900743	Phase 2	Completed	219	Regorafenib (not pazopanib) in metastatic soft tissue sarcoma post-anthracycline — same drug class, indirect evidence only
NCT02048371	Phase 2	Completed	131	SARC024: oral regorafenib across sarcoma subtypes — indirect, different drug
NCT06263231	Phase 3	Active, not recruiting	333	Intratumoral INT230-6 vs. US standard of care in soft tissue sarcomas — different drug class, low relevance

Literature Evidence

PMID	Year	Type	Journal	Key Findings
28844815	2017	RCT (PALETTE subgroup analysis)	The Lancet. Oncology	Commentary on pazopanib activity specifically in the liposarcoma subgroup of the pivotal PALETTE trial
33355646	2021	Phase 2 RCT (PAPAGEMO, final results)	JAMA Oncology	Efficacy of pazopanib with/without gemcitabine in anthracycline/ifosfamide-refractory soft tissue sarcoma
36890471	2023	RCT protocol (Phase 2, JCOG1802)	BMC Cancer	Randomized comparison of trabectedin, eribulin, and pazopanib as second-line therapy for advanced soft tissue sarcoma
35609512	2022	Review	Oncology Research and Treatment	Overview of established and experimental systemic treatments for advanced liposarcoma, including pazopanib
32026050	2020	Review	Current Treatment Options in Oncology	Systemic therapy options for dedifferentiated liposarcoma
34050255	2021	Phase 2, single-arm	British Journal of Cancer	Pazopanib with oral topotecan active in refractory soft tissue sarcoma, prolongs PFS
28832986	2017	Phase 2, prospective single-arm	Cancer	Single-agent pazopanib shows treatment activity and manageable safety in unresectable/metastatic liposarcoma
31010343	2019	Cohort / subgroup analysis	Expert Opinion on Investigational Drugs	Review of pazopanib’s anti-angiogenic activity in advanced intermediate/high-grade liposarcoma
34356494	2021	Translational / pathology study	Biology	Molecular profiling of soft tissue sarcoma samples before/after neoadjuvant pazopanib (GISG-04/NOPASS)
25500074	2014	Preclinical (xenograft)	Translational Oncology	Pazopanib suppresses tumour growth via anti-angiogenesis in dedifferentiated liposarcoma xenograft models

Denmark Market Information

Pazopanib currently has no marketing authorisation on file in Denmark (market status: Not marketed; 0 authorisations recorded). No Laegemiddelstyrelsen or EMA centralised licence data is available in this evidence pack to summarize.

Cytotoxicity

Pazopanib’s oncology use (renal cell carcinoma, soft tissue sarcoma) qualifies it for this section, though local toxicity/category data was not returned by DrugBank for this pack.

Item	Content
Cytotoxicity Classification	Targeted therapy (multi-target receptor tyrosine kinase inhibitor — VEGFR/PDGFR/c-KIT; based on known pharmacology, not local database)
Myelosuppression Risk	Please refer to the Summary of Product Characteristics (SmPC) — TKIs as a class typically carry lower myelosuppression risk than conventional cytotoxic chemotherapy, but drug-specific hematologic data is not in this evidence pack
Emetogenicity Classification	Please refer to the SmPC
Monitoring Items	Please refer to the SmPC — general TKI monitoring commonly includes blood pressure, liver function tests, CBC, and QT interval
Handling Protection	Please refer to the SmPC and institutional oral-oncolytic handling policy

Safety Considerations

Please refer to the approved Summary of Product Characteristics (SmPC) for safety information — key warnings, contraindications, and drug-interaction data for pazopanib were not available in this evidence pack (data gap DG001, Blocking).

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: Multiple pazopanib-specific Phase 2 trials — including two dedicated to liposarcoma monotherapy (NCT01692496, NCT01506596) — plus PALETTE-trial subgroup literature support biological activity in liposarcoma. However, pazopanib is not currently marketed in Denmark and local safety/label data is entirely missing, so this cannot proceed without further work.

To proceed, the following is needed:

Danish/EU SmPC warnings, contraindications, and DDI data (DG001, Blocking)
Confirmed mechanism-of-action documentation from DrugBank (DG002, High)
A Danish or EU marketing-authorisation pathway assessment, since pazopanib currently has zero licences on file here
Direct citation and full data extraction from the PALETTE Phase 3 RCT (referenced only indirectly via PMID 28844815)
Clarification of applicability across liposarcoma histologic subtypes (well-differentiated/dedifferentiated/myxoid/pleomorphic), since trial populations were heterogeneous
Disclaimer

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