Pazopanib

Evidence Level: L3

Predicted Indications: 6

Pazopanib

Pharmacist Assessment Report

Pazopanib: Liposarcoma

One-Sentence Summary

Pazopanib is a multi-targeted tyrosine kinase inhibitor originally used for renal cell carcinoma (clear cell type) and advanced soft tissue sarcoma. Among the other predictions, liposarcoma has the most mature evidence (6 trials, Phase 2 data).

Quick Overview

Item	Content
Original Indication	Not recorded in the local data
Predicted New Indication	Liposarcoma
TxGNN Prediction Score	0.9959
Evidence Level	L3
Canada Market Status	Marketed (marketed DINs: 3 of 3)
Number of DINs	3 (marketed: 3)
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available from the compiled data. Based on known information, pazopanib is a multi-targeted inhibitor of VEGFR, PDGFR and c-KIT. Its efficacy in clear cell renal cell carcinoma and advanced soft tissue sarcoma has been established.

Non-clear-cell and unclassified renal cell carcinoma often remain dependent on the VEGF pathway. The anti-angiogenic activity of pazopanib may therefore carry over to these subtypes. The supporting evidence comes from retrospective and real-world cohorts and one single-arm multicenter Phase 2 study. No Phase 3 RCT exists for this population.

The other predicted indications follow similar logic:

Liposarcoma and fibroblastic tumors: pazopanib is approved for advanced soft tissue sarcoma, and the registration trial excluded liposarcoma. Liposarcoma-specific Phase 2 data exist, but activity appears to vary by subtype.
Dermatofibrosarcoma protuberans (DFSP): this tumour is driven by the COL1A1-PDGFB fusion, which activates PDGFR, a pazopanib target. This gives a strong mechanistic rationale, especially for imatinib-resistant disease.

Clinical Trial Evidence

For the next best-supported prediction, liposarcoma, the main trials are:

Trial Number	Phase	Status	Enrollment	Key Findings
NCT01506596	Phase 2	Completed	42	Single-agent pazopanib in unresectable or metastatic liposarcoma
NCT01692496	Phase 2	Completed	52	Activity and tolerability of pazopanib in advanced or metastatic liposarcoma after standard therapy
NCT02357810	Phase 2	Completed	178	Pazopanib plus oral topotecan in metastatic soft tissue and bone sarcomas
NCT02180867	Phase 2/3	Completed	140	Neoadjuvant radiation ± pazopanib in non-rhabdomyosarcoma soft tissue sarcoma
NCT01532687	Phase 2	Completed	54	Randomized, double-blind: gemcitabine ± pazopanib in refractory soft tissue sarcoma
NCT06239272	Phase 1/2	Recruiting	139	Risk-adapted study with maintenance pazopanib in non-rhabdomyosarcoma soft tissue sarcoma (young patients)

For DFSP, the directly relevant trial is NCT01059656 (Phase 2, Terminated, 23 patients). It tested pazopanib in unresectable, locally advanced DFSP.

For fibroblastic neoplasm, NCT02066285 (Phase 2, Completed, 96 patients) tested single-agent pazopanib in solitary fibrous tumor and extraskeletal myxoid chondrosarcoma.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
28546525	2018	Phase 2 (single-arm)	Cancer Res Treat	Multicenter open-label study of pazopanib efficacy and safety in non-clear-cell RCC
28108284	2017	Retrospective cohort	Clin Genitourin Cancer	Italian PANORAMA study of first-line pazopanib in non-clear-cell RCC
27568124	2017	Retrospective cohort	Clin Genitourin Cancer	Outcomes of metastatic non-clear-cell RCC treated with pazopanib
31921344	2019	Real-world study	Ecancermedicalscience	Sunitinib vs pazopanib in non-clear-cell and sarcomatoid RCC
41558869	2026	Retrospective cohort	Eur Urol Oncol	IMDC outcomes of first-line therapies in metastatic non-clear-cell RCC by histologic subtype
30268423	2019	Retrospective cohort	Clin Genitourin Cancer	CUP with RCC features treated with targeted therapy

Other predicted indications (selected):

PMID	Year	Type	Journal	Key Findings
32956651	2021	Phase 2	J Invest Dermatol	Multicenter Phase 2 of pazopanib in unresectable DFSP
31010343	2019	Phase 2 summary	Expert Opin Investig Drugs	Pazopanib in intermediate/high-grade advanced liposarcoma
34050255	2021	Phase 2	Br J Cancer	Pazopanib with oral topotecan in metastatic soft tissue and bone sarcomas
25269954	2014	Preclinical and clinical	Eur J Cancer	Activity of pazopanib in solitary fibrous tumour
38759389	2024	Real-world study	Eur J Cancer	Pazopanib and sorafenib in desmoid tumors (CanSaRCC)
28844815	2017	Commentary	Lancet Oncol	Pazopanib for advanced liposarcoma

Canada Market Information

DIN	Product Name	Dosage Form	Approved Indication
02352303	VOTRIENT	Not specified	Not specified
02552957	AURO-PAZOPANIB	Not specified	Not specified
02525666	PMS-PAZOPANIB	Not specified	Not specified

Cytotoxicity

Item	Content
Cytotoxicity Classification	Targeted therapy (multi-targeted tyrosine kinase inhibitor), not a conventional cytotoxic
Myelosuppression Risk	Please refer to the package insert warnings and precautions
Emetogenicity Classification	Please refer to the package insert warnings and precautions
Monitoring Items	Liver function, blood pressure, ECG/QT and electrolytes, thyroid function, urine protein and blood counts. These are suggested from the contraindication and interaction signals below and should be confirmed against the package insert.
Handling Protection	Please refer to the package insert warnings and precautions

Safety Considerations

Contraindications and risk conditions (from the knowledge graph, not label text):

Cardiovascular: hypertension, long QT syndrome (including familial), torsades de pointes, myocardial infarction, coronary thrombosis
Hepatic: liver failure, drug-induced liver injury, hyperbilirubinemia (including Gilbert syndrome)
Endocrine and metabolic: hypothyroidism, myxedema, potassium deficiency, hypercalcemia, nephrocalcinosis, phosphorus metabolism disorders
Bleeding and gastrointestinal: intracerebral hemorrhage, active peptic ulcer disease, pancreatitis, diarrheal disease
Other: proteinuria, hemoglobinopathy

Drug Interactions (100 interactions in total; the main ones listed):

Major: acid-suppressing drugs (famotidine, ranitidine, cimetidine, omeprazole, esomeprazole, rabeprazole, dexlansoprazole), clarithromycin and dolasetron
Moderate: pioglitazone, saxagliptin, loperamide, aprepitant, dexamethasone, budesonide, bisacodyl, magnesium oxide, polyethylene glycol and eliglustat

Package insert warnings and contraindications were not available in the compiled data. Please refer to the Health Canada package insert for official safety information.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale:

For unclassified renal cell carcinoma, a single-arm Phase 2 study and several retrospective and real-world cohorts support the use of pazopanib. This is a mechanistic extension of an approved RCC indication, but no registered trials or Phase 3 RCTs exist (Evidence Level L3).
Liposarcoma (L2, Proceed with Guardrails) has the most mature evidence among the other predictions. DFSP and fibroblastic neoplasm have Phase 2 data but are best treated as research questions. The remaining predictions (Xp11.2/TFE3 RCC, RCC associated with neuroblastoma, childhood kidney cell carcinoma, ovarian myxoid liposarcoma, heart fibrosarcoma and kidney fibrosarcoma) rest on model scores alone and should be held.

To proceed, the following is needed:

Health Canada package insert warnings and contraindications (a blocking gap for safety screening)
Detailed mechanism of action data from DrugBank
Health Canada approved indication text and dosage forms for the three DINs
Prospective data, ideally a registered trial, in unclassified or non-clear-cell RCC
A safety monitoring plan for blood pressure, QT interval, liver function and acid-suppressant interactions
A review of the liposarcoma subtype-specific Phase 2 results and of the Canadian reimbursement context
Disclaimer

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