Axitinib

證據等級: L5

預測適應症: 10 個

Axitinib: From Advanced Renal Cell Carcinoma to Renal Cell Carcinoma Associated with Neuroblastoma

One-Sentence Summary

Axitinib (Inlyta®) is a selective VEGFR-1/2/3 tyrosine kinase inhibitor approved for the second-line treatment of advanced renal cell carcinoma (RCC), currently marketed in Malaysia with 2 registered products. The TxGNN model’s highest-ranked prediction is renal cell carcinoma associated with neuroblastoma (score 99.90%), an extremely rare RCC variant with currently no supporting clinical trials or published literature. This is a multi-indication evaluation covering 10 TxGNN predictions; the most evidence-supported candidate is renal carcinoma (Rank 6, L1 level, 20 publications including multiple Phase 3 RCTs), while Xp11.2/TFE3-translocation RCC, childhood RCC, and collecting duct carcinoma carry active Phase 2 trial support.

Quick Overview

Item	Content
Original Indication	Advanced Renal Cell Carcinoma (second-line; derived from known approved use)
Predicted New Indication	Renal Cell Carcinoma Associated with Neuroblastoma
TxGNN Prediction Score	99.90%
Evidence Level	L5 (model prediction only, no clinical studies)
Malaysia Market Status	✓ Marketed
Number of Registrations	2
Recommended Decision	Hold (Rank 1) — see multi-indication summary for full picture

Why Is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available in this evidence pack. Based on clinical literature referenced within this report, Axitinib is a selective second-generation VEGFR-1/2/3 tyrosine kinase inhibitor (TKI). It works by blocking VEGFR signaling to suppress tumor angiogenesis — the key growth mechanism in most renal cell carcinoma subtypes. This activity has been confirmed in multiple Phase 3 randomized controlled trials (KEYNOTE-426, JAVELIN Renal 101, RENOTORCH), leading to FDA approval as a second-line RCC agent and current Malaysia market approval.

The TxGNN model assigns high scores across multiple RCC subtypes because renal cell carcinoma broadly depends on VEGF/VEGFR-driven angiogenesis. The top prediction — RCC associated with neuroblastoma — is an extremely rare entity (only a handful of reported cases worldwide) that shares the broader RCC disease node in the knowledge graph. The high TxGNN score is most plausibly explained by graph-proximity to better-studied RCC subtypes rather than direct mechanistic or clinical evidence for this specific variant.

For RCC subtypes with demonstrated molecular evidence of VEGFR pathway activation — notably Xp11.2/TFE3-translocation RCC (mTOR-VEGF axis upregulation) and collecting duct carcinoma (partial VEGFR overexpression reported) — the mechanistic rationale is substantially stronger and is being actively tested in clinical trials.

Clinical Trial Evidence

Primary prediction (Rank 1): renal cell carcinoma associated with neuroblastoma

Currently no related clinical trials registered.

For clinical trial evidence across all 10 predicted indications, see the All Predicted Indications Summary section below.

Literature Evidence

Primary prediction (Rank 1): renal cell carcinoma associated with neuroblastoma

Currently no related literature available.

For literature evidence across all 10 predicted indications, see the All Predicted Indications Summary section below.

All Predicted Indications Summary

This evidence pack is a multi-indication evaluation (ID: TW-DB06626-multi) covering 10 TxGNN predictions. Below is a consolidated overview followed by the clinical evidence for each actionable prediction.

Prediction Overview

Rank	Predicted Indication	TxGNN Score	Evidence Level	Decision
1	Renal cell carcinoma associated with neuroblastoma	99.90%	L5	Hold
2	RCC with Xp11.2 translocations/TFE3 gene fusions	99.90%	L2	Research Question
3	Unclassified renal cell carcinoma	99.90%	L3	Research Question
4	Childhood kidney cell carcinoma	99.87%	L2	Research Question
5	Liposarcoma	99.87%	L5	Hold
6	Renal carcinoma	99.85%	L1	Proceed with Guardrails
7	Ovarian myxoid liposarcoma	99.84%	L5	Hold
8	Angiolipoma	99.83%	L5	Hold
9	Collecting duct carcinoma	99.81%	L3	Research Question
10	Familial spontaneous pneumothorax	99.78%	L5	Hold

Clinical Trial Evidence — Rank 2: Xp11.2/TFE3 RCC & Rank 4: Childhood RCC

Trial Number	Phase	Status	Enrollment	Key Findings
NCT03595124	Phase 2	Active, Not Recruiting	15	Randomized trial of axitinib + nivolumab vs. nivolumab monotherapy for TFE/translocation RCC across all age groups; directly addresses both Xp11.2 RCC and pediatric RCC (Xp11.2 subtype accounts for ~60–70% of childhood RCC)
NCT04510597	Phase 3	Recruiting	364	PROBE Trial: immunotherapy ± cytoreductive nephrectomy for metastatic RCC; primarily adult population but validates ICI + VEGFR TKI framework applicable to pediatric RCC subgroups

Clinical Trial Evidence — Rank 3: Unclassified RCC

Trial Number	Phase	Status	Enrollment	Key Findings
NCT04033991	Real-World Study	Completed	684	UK retrospective study of sunitinib (1L) → axitinib (2L) sequencing across metastatic/advanced RCC histologies; subgroup analysis could yield data on unclassified RCC
NCT02156895	Post-Marketing Surveillance	Completed	111	Safety and efficacy monitoring for axitinib in routine clinical practice across all RCC subtypes

Clinical Trial Evidence — Rank 9: Collecting Duct Carcinoma

Trial Number	Phase	Status	Enrollment	Key Findings
NCT06211114	Phase 2	Recruiting	30	Directly designed for previously treated advanced collecting duct carcinoma using immune checkpoint inhibitor + axitinib combination; trial initiation itself demonstrates mechanistic rationale is recognized by the research community

Literature Evidence — Rank 6: Renal Carcinoma (L1 — Strongest Evidence)

Note: This prediction reflects Axitinib’s known approved indication. The L1 evidence below validates the TxGNN model’s accuracy.

PMID	Year	Type	Journal	Key Findings
30779529	2019	Phase 3 RCT (KEYNOTE-426)	N Engl J Med	Pembrolizumab + axitinib showed superior OS, PFS, and ORR versus sunitinib as first-line treatment for advanced RCC
37500340	2023	Phase 3 RCT 43-month follow-up	European Urology	Long-term KEYNOTE-426 results confirm durable OS and PFS benefit for pembrolizumab + axitinib
40750932	2025	Phase 3 RCT 5-year analysis	Nature Medicine	5-year KEYNOTE-426 analysis with prespecified biomarker data confirms durable clinical benefit
30779531	2019	Phase 3 RCT (JAVELIN Renal 101)	N Engl J Med	Avelumab + axitinib significantly prolonged PFS versus sunitinib in previously untreated advanced RCC
39706335	2025	Phase 3 RCT final analysis (JAVELIN Renal 101)	Ann Oncol	Final OS analysis of JAVELIN Renal 101; overall survival primary endpoint results reported
37872020	2024	Phase 3 RCT (RENOTORCH)	Ann Oncol	Toripalimab + axitinib vs. sunitinib for intermediate/poor-risk advanced RCC; supports ICI + axitinib as a platform
33284113	2020	Phase 3 RCT extended follow-up	Lancet Oncol	KEYNOTE-426 extended follow-up: sustained efficacy and safety of pembrolizumab + axitinib over sunitinib
32895571	2020	Phase 3 RCT biomarker analysis	Nature Medicine	Molecular analyses of JAVELIN Renal 101 (n=886); PD-L1 and tumor mutational burden were not predictive of PFS
29033542	2017	Drug Review	Drug Des Devel Ther	Axitinib pharmacology, development, and clinical positioning as second-generation VEGFR TKI in RCC
28276433	2017	Disease Review	Nat Rev Dis Primers	Comprehensive overview of RCC biology, molecular subtypes, and treatment landscape

Literature Evidence — Rank 4: Childhood RCC

PMID	Year	Type	Journal	Key Findings
31012542	2019	Review	Pediatr Blood Cancer	Review of treatment options for advanced pediatric RCC; highlights lack of standardized therapy and context for VEGFR TKI use
26279736	2015	Case Report	Can Urol Assoc J	First reported axitinib use in a child (12-year-old) with malignant epithelioid angiomyolipoma; authors conclude adult protocols can be safely applied in this rare pediatric case

Malaysia Market Information

Axitinib has 2 registered products in the Malaysian market. Detailed registration records (product name, dosage form, manufacturer, and approved indication text) are not currently available in the evidence database and require direct verification with NPRA.

Item	Status
Market Status	✓ Marketed
Number of Registrations	2
Product Details	Not available — please verify via NPRA official database

Cytotoxicity

Axitinib is an anticancer agent indicated for renal cell carcinoma.

Item	Content
Cytotoxicity Classification	Targeted therapy — Selective VEGFR-1/2/3 tyrosine kinase inhibitor (TKI); not a conventional cytotoxic chemotherapy agent
Myelosuppression Risk	Please refer to the package insert warnings and precautions
Emetogenicity Classification	Please refer to the package insert warnings and precautions
Monitoring Items	Please refer to the package insert warnings and precautions
Handling Protection	Standard precautions for oral targeted therapy; consult institutional cytotoxic drug handling guidelines

Safety Considerations

Please refer to the package insert for safety information.

Full safety data (warnings, contraindications, and drug interactions) are not available in the current evidence pack. Retrieval of the product package insert (SOP remediation item DG001) is required before clinical decision-making.

Conclusion and Next Steps

Decision: Hold (Rank 1: RCC Associated with Neuroblastoma) / Proceed with Guardrails (Rank 6: Renal Carcinoma)

Rationale:

The top TxGNN prediction (RCC associated with neuroblastoma, L5) has no clinical or published evidence and represents an ultra-rare entity; a “Hold” decision is appropriate until any case-level data emerges.
The strongest evidence sits at Rank 6 (renal carcinoma, L1), supported by multiple completed Phase 3 RCTs — this represents Axitinib’s approved indication and confirms the model’s face validity.
RCC subtypes at Ranks 2, 4, and 9 (Xp11.2/TFE3 RCC, childhood RCC, collecting duct carcinoma) have active Phase 2 trials and carry mechanistic rationale; these are appropriate “Research Question” candidates to monitor.
Predictions with L5 evidence and no mechanistic link to VEGFR (liposarcoma, ovarian myxoid liposarcoma, angiolipoma, familial spontaneous pneumothorax) should remain on “Hold.”

To proceed, the following is needed:

Retrieve NPRA full registration records for both Axitinib products (product names, dosage forms, approved indications)
Obtain detailed MOA data from DrugBank API (data gap DG002) to strengthen mechanistic analysis
Download and parse the product package insert PDF to extract warnings and contraindications (data gap DG001 — currently blocks safety pre-screening)
Monitor NCT03595124 results (Xp11.2/TFE3 RCC, expected completion November 2026) as this will provide pivotal evidence for Ranks 2 and 4
Monitor NCT06211114 results (collecting duct carcinoma, expected completion February 2027)
Before any off-label use in pediatric patients (Rank 4), obtain pediatric pharmacokinetic data and confirm dosing guidance

This report is for research reference only and does not constitute medical advice. Drug repurposing candidates require clinical validation before application.

Disclaimer

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