Pazopanib

證據等級: L5

預測適應症: 10 個

Pazopanib: From Non-Adipocytic Soft Tissue Sarcoma to Liposarcoma

One-Sentence Summary

Pazopanib is a multi-target tyrosine kinase inhibitor with established efficacy in clear-cell renal cell carcinoma and non-adipocytic soft tissue sarcoma. The TxGNN model predicts it may also be effective for Liposarcoma, a soft-tissue sarcoma subtype currently outside its labeled use, with 9 clinical trials and 20 publications currently supporting this direction, including two dedicated completed Phase 2 studies.

Quick Overview

Item	Content
Original Indication	Clear-cell renal cell carcinoma; non-adipocytic soft tissue sarcoma (derived from literature context — no formal regulatory record available)
Predicted New Indication	Liposarcoma
TxGNN Prediction Score	99.59%
Evidence Level	L2
Norway Market Status	Not marketed
Number of Authorizations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data for pazopanib is not available from the primary sources queried (DrugBank query returned a data gap). Based on information embedded in the clinical trial and literature evidence, pazopanib is a multi-target tyrosine kinase inhibitor (VEGFR, PDGFR-α/β, c-KIT) with anti-angiogenic and antitumorigenic properties. Its efficacy in clear-cell renal cell carcinoma and non-adipocytic advanced/metastatic soft tissue sarcoma is well established — it is already approved for these uses and cited repeatedly across the literature as "a standard first-line treatment" in these settings.

Liposarcoma is a soft tissue sarcoma subtype that was historically excluded from pazopanib's approved label (the pivotal PALETTE trial excluded adipocytic sarcomas), but it shares the same mesenchymal lineage and overlapping molecular drivers as non-adipocytic STS. PDGFR-α/β signaling is implicated in liposarcoma proliferation, particularly in the dedifferentiated subtype, and VEGFR-driven angiogenesis supports tumor growth across STS subtypes generally. This provides a plausible mechanistic bridge from the approved indication to the predicted one.

Supporting this rationale, two dedicated Phase 2 trials (NCT01506596, NCT01692496) specifically enrolled unresectable/metastatic liposarcoma patients to test single-agent pazopanib, and their results were published in peer-reviewed literature (PMID 28832986, Cancer 2017). Preclinical xenograft data (PMID 25500074) further demonstrate pazopanib-mediated tumor regression through anti-angiogenic action in dedifferentiated liposarcoma models, reinforcing the biological plausibility of the prediction.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT01506596	Phase 2	Completed	42	Single-agent pazopanib efficacy and safety in unresectable or metastatic liposarcoma
NCT01532687	Phase 2	Completed	54	Gemcitabine ± pazopanib in refractory soft tissue sarcoma, including a liposarcoma subgroup
NCT02180867	Phase 2/3	Active, not recruiting	140	Preoperative chemoradiation ± pazopanib in non-rhabdomyosarcoma STS (includes liposarcoma subtype)
NCT06239272	Phase 1/2	Recruiting	139	Maintenance pazopanib with dose-escalated radiation and selinexor in non-rhabdomyosarcoma STS
NCT02357810	Phase 2	Completed	178	Pazopanib + oral topotecan in metastatic/non-resectable soft tissue and bone sarcomas
NCT06263231	Phase 3	Active, not recruiting	333	INT230-6 vs. US standard of care in liposarcoma/UPS/leiomyosarcoma (pazopanib not the study drug)
NCT01692496	Phase 2	Completed	52	Pazopanib activity/tolerability in advanced/metastatic liposarcoma relapsed after standard therapy
NCT01900743	Phase 2	Completed	219	Regorafenib vs. placebo in metastatic STS after anthracycline failure (liposarcoma cohort; pazopanib not the study drug)
NCT02048371	Phase 2	Completed	131	SARC024: oral regorafenib across selected sarcoma subtypes, referencing prior pazopanib activity in STS

Literature Evidence

PMID	Year	Type	Journal	Key Findings
34050255	2021	RCT	British Journal of Cancer	Pazopanib is active in refractory STS and significantly prolongs progression-free survival; combination with topotecan studied
31010343	2019	Cohort (Phase 2 subgroup)	Expert Opinion on Investigational Drugs	Reviews pazopanib's anti-angiogenic/antitumorigenic activity specifically in liposarcoma, a subtype lacking effective treatment options
33355646	2021	Cohort	JAMA Oncology	PAPAGEMO trial final results: pazopanib ± gemcitabine in anthracycline/ifosfamide-refractory STS
28832986	2017	Phase 2 study	Cancer	Prospective single-arm Phase 2 study determining treatment activity and safety of single-agent pazopanib in unresectable/metastatic liposarcoma
28844815	2017	Review	The Lancet Oncology	Commentary on pazopanib's role for advanced liposarcoma
35609512	2022	Review	Oncology Research and Treatment	Established and experimental systemic treatment options across liposarcoma subtypes
32026050	2020	Review	Current Treatment Options in Oncology	Systemic therapy options for dedifferentiated liposarcoma
37298520	2023	Review	International Journal of Molecular Sciences	Treatment landscape for dedifferentiated liposarcoma in the immunotherapy era
25500074	2014	Preclinical	Translational Oncology	Pazopanib suppresses tumor growth via anti-angiogenesis in dedifferentiated liposarcoma xenograft models
30060824	2018	Case report	Tissue & Cell	PDGFRA-amplified pleomorphic liposarcoma PDOX model regressed by pazopanib after doxorubicin resistance

Norway Market Information

Pazopanib is currently not marketed in Norway; no authorization or license records are available in the evidence pack (total_licenses: 0).

Cytotoxicity

Item	Content
Cytotoxicity Classification	Targeted therapy — multi-target tyrosine kinase inhibitor (VEGFR/PDGFR/c-KIT) with anti-angiogenic activity (per literature context in evidence pack)
Myelosuppression Risk	Not available in current evidence pack — please refer to the package insert warnings and precautions
Emetogenicity Classification	Not available in current evidence pack — please refer to the package insert warnings and precautions
Monitoring Items	Not available in current evidence pack — please refer to the package insert warnings and precautions
Handling Protection	Not available in current evidence pack — please refer to the package insert warnings and precautions

Safety Considerations

Please refer to the package insert for safety information. (Key warnings, contraindications, and drug interaction data were flagged as data gaps in this evidence pack — TFDA label parsing is required to close this gap.)

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: Two dedicated completed Phase 2 trials (NCT01506596, NCT01692496) and their published results (PMID 28832986) directly support single-agent pazopanib activity in unresectable/metastatic liposarcoma, reinforced by preclinical mechanistic data and multiple supportive reviews — meeting the L2 evidence bar, but falling short of confirmatory Phase 3 data.

To proceed, the following is needed:

TFDA/Norwegian label data (warnings, contraindications, DDI) — currently a blocking data gap for safety pre-screening
Formal DrugBank MOA confirmation to substantiate the PDGFR/VEGFR mechanistic rationale
A confirmatory randomized trial in liposarcoma (current evidence is single-arm Phase 2 only)
Norway/EU market authorization pathway assessment, as the drug is not currently marketed in this jurisdiction

Note: This TxGNN screen also flagged dermatofibrosarcoma protuberans (rank 10, evidence level L2, "Proceed with Guardrails") as a second candidate with comparable evidence strength (a dedicated Phase 2 trial and a multicenter Phase 2 publication), driven by the same PDGFR-targeting mechanism. This may warrant a separate evaluation.

Disclaimer

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