Pazopanib

證據等級: L5

預測適應症: 10 個

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

One-Sentence Summary

Pazopanib is a multi-target tyrosine kinase inhibitor whose established use — as documented in the retrieved literature — is advanced/metastatic clear-cell renal cell carcinoma (ccRCC) and non-adipocytic soft tissue sarcoma. The TxGNN model predicts it may also be effective for Unclassified Renal Cell Carcinoma, with 1 completed Phase 3 clinical trial and 6 publications currently supporting this direction. Note: the drug is not currently marketed in Germany, and TFDA-level warning/contraindication data is a blocking gap for safety pre-assessment.

Quick Overview

Item	Content
Original Indication	Not populated in the evidence pack (`taiwan_regulatory.licenses` and `drug.original_indications` are both empty). Based on retrieved literature within this pack, pazopanib is a registered/standard therapy for advanced/metastatic clear-cell RCC and non-adipocytic soft tissue sarcoma.
Predicted New Indication	Unclassified Renal Cell Carcinoma
TxGNN Prediction Score	99.63%
Evidence Level	L2 (1 completed Phase 3 trial + multiple retrospective/real-world cohorts)
Germany Market Status	✗ Not Marketed
Number of Authorizations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available (original_moa: [Data Gap]). Based on the retrieved literature itself, pazopanib is a multi-target tyrosine kinase inhibitor with anti-angiogenic activity; multiple abstracts in the evidence pack describe it as a "standard first-line treatment for metastatic clear-cell renal cell carcinoma (ccRCC)" (PMID 28108284) and note it is "registered" for advanced RCC (NCT01613846 summary).

Unclassified RCC is a rare, non-clear-cell histologic subtype within the same organ/tumor family as pazopanib's established indication. Because treatment approaches for non-clear-cell RCC (nccRCC) are "frequently extrapolated from data of clear cell renal cell carcinoma" (PMID 31921344), and pazopanib's anti-angiogenic mechanism is not histology-restricted, the mechanistic rationale for extending use into unclassified/non-clear-cell RCC is plausible and is echoed across several retrospective cohorts (PANORAMA study, PMID 28108284; MD Anderson cohort, PMID 27568124; IMDC consortium analysis, PMID 41558869).

However, "unclassified RCC" is a distinct and rarer diagnostic category than the nccRCC populations actually studied in these papers, and no trial or publication in this pack specifically isolates the "unclassified" subtype. This introduces residual uncertainty about direct applicability.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT01613846	Phase 3	Completed	544	Randomized sequential trial evaluating sorafenib→pazopanib vs. pazopanib→sorafenib in advanced/metastatic RCC; both agents were registered/effective in RCC but no prior comparative sequencing data existed.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
28546525	2018	Phase II, single-arm	Cancer Research and Treatment	Prospective phase II study assessing efficacy/safety of pazopanib specifically in non-clear-cell RCC (nccRCC).
31921344	2019	Real-world/Retrospective	Ecancermedicalscience	Compares first-line sunitinib vs. pazopanib in non-clear-cell and sarcomatoid histology mRCC; asks whether the two are interchangeable.
28108284	2017	Retrospective multicenter	Clinical Genitourinary Cancer	Italian PANORAMA study: retrospective efficacy/toxicity analysis of first-line pazopanib in nccRCC.
27568124	2017	Retrospective cohort	Clinical Genitourinary Cancer	Outcomes of metastatic non-clear-cell RCC patients treated with pazopanib.
30268423	2019	Retrospective/Case series	Clinical Genitourinary Cancer	Histologic/immunohistochemical characterization and targeted-therapy outcomes in carcinoma-of-unknown-primary presenting with mRCC features (CUP-mRCC).
41558869	2026	Retrospective database cohort	European Urology Oncology	IMDC consortium analysis comparing contemporary vs. traditional first-line therapies across nccRCC histologic subtypes, including unclassified RCC.

Germany Market Information

Pazopanib currently holds no marketing authorization in Germany (market status: Not marketed; 0 authorizations on file).

Cytotoxicity

Pazopanib's established indications (renal cell carcinoma, soft tissue sarcoma) are antineoplastic, and it is a multi-target tyrosine kinase inhibitor — classifying it under this section.

Item	Content
Cytotoxicity Classification	Targeted therapy (multi-target tyrosine kinase inhibitor; anti-angiogenic, VEGFR/PDGFR/c-KIT-directed) — not a conventional cytotoxic agent
Myelosuppression Risk	Not specifically documented in this evidence pack; TKIs of this class are generally associated with lower myelosuppression risk than conventional cytotoxics — please refer to the package insert
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. (key_warnings, contraindications, and DDI query all returned no data — DDI query status: not_found.)

Note: This is flagged in the evidence pack as a Blocking data gap (DG001 — TFDA warning/contraindication labeling not yet retrieved), meaning this candidate cannot yet pass S1 safety pre-assessment.

Other Predicted Indications (Summary)

For context, the same evidence pack scored 9 additional candidate indications for pazopanib. Most have weak or no direct evidence and are held; two related sarcoma indications show notably stronger, disease-specific support:

Rank	Disease	TxGNN Score	Evidence Level	Recommendation
2	Renal cell carcinoma (Xp11.2/TFE3 fusion)	99.63%	L5	Hold — no trial/literature support
3	Renal cell carcinoma with neuroblastoma	99.63%	L5	Hold — no trial/literature support
4	Liposarcoma	99.59%	L2	Proceed with Guardrails — 2 disease-specific Phase II trials (NCT01506596, NCT01692496) + randomized Phase II combo trial (NCT01532687); PDGFRA-amplification mechanistic rationale
5	Childhood kidney cell carcinoma	99.54%	L4	Hold — only trial listed is an adult mRCC study, likely ontology mismatch; no pediatric PK/safety data
6	Ovarian myxoid liposarcoma	99.51%	L5	Hold — no trial/literature support
7	Heart fibrosarcoma	99.37%	L4	Hold — only broad STS trials, no cardiac-specific data; cardiotoxicity risk needs evaluation
8	Fibroblastic neoplasm	99.35%	L3 (est.)	Hold — rich literature on desmoid tumor/solitary fibrous tumor subtypes (incl. single-arm Phase II, PMID 30578023) but "fibroblastic neoplasm" as a category is too broad/heterogeneous for a single recommendation
9	Kidney fibrosarcoma	99.33%	L5	Hold — no trial/literature support
10	Dermatofibrosarcoma protuberans	99.29%	L2 (est.)	Proceed with Guardrails (cautious) — disease-specific Phase II trial (NCT01059656, terminated) + multicenter Phase II publication (PMID 32956651); strong mechanistic rationale via COL1A1-PDGFB fusion

Conclusion and Next Steps

Decision: Hold

Rationale: Efficacy evidence for the top prediction (unclassified RCC) is moderate (L2) and mechanistically plausible, and two other candidates (liposarcoma, dermatofibrosarcoma protuberans) show even stronger disease-specific trial evidence. However, this candidate cannot advance because (1) TFDA-level warnings/contraindications are a Blocking data gap that prevents safety pre-assessment (S1), and (2) the drug currently has zero marketing authorizations in Germany, so regulatory pathway and local labeling are undefined.

To proceed, the following is needed:

Retrieve TFDA/BfArM package insert (warnings, contraindications, DDI) to resolve DG001 before any safety pre-assessment
Obtain formal DrugBank/MOA data to resolve DG002 and support mechanistic-link scoring
Confirm regulatory pathway given 0 current marketing authorizations in Germany
If pursuing liposarcoma or dermatofibrosarcoma protuberans in parallel, prioritize these given stronger disease-specific Phase II evidence
Disclaimer

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