Erlotinib
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Erlotinib: From Non-Small Cell Lung Cancer to Ewing Sarcoma
One-Sentence Summary
Erlotinib is an EGFR (HER1) tyrosine kinase inhibitor most widely known as an anticancer agent (per attached literature, e.g. PMID 32164971). The TxGNN model predicts it may be effective for Ewing Sarcoma, currently supported by 1 clinical trial (withdrawn, 0 enrolled) and 2 publications, with no completed trial data confirming efficacy.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | No regulatory record available in this evidence pack (taiwan_regulatory.licenses empty; general anticancer/NSCLC use noted only in cross-referenced literature, not sourced from regulatory data) |
| Predicted New Indication | Ewing Sarcoma |
| TxGNN Prediction Score | 95.77% |
| Evidence Level | L4 |
| EU Market Status | Not Marketed (Not marketed) |
| Number of Authorizations | 0 |
| Recommended Decision | Research Question (Decision Stage S1) |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available (data gap DG002, severity High). Based on information embedded in the evidence pack’s rationale and cross-referenced literature, Erlotinib is an EGFR (HER1) tyrosine kinase inhibitor (EGFR-TKI) whose known anticancer activity operates by blocking EGFR-driven proliferation signaling.
The system’s own repurposing rationale for this prediction states: some Ewing sarcoma tumors express EGFR/HER3, so an EGFR-TKI could theoretically show activity. However, Ewing sarcoma is primarily driven by the EWSR1-FLI1 fusion oncoprotein rather than EGFR signaling, making this mechanistic link indirect and relatively weak rather than a primary driver-pathway match.
Consistent with this weak/indirect link, the only related clinical trial identified (NCT02689336) was a genomically-targeted pediatric basket trial requiring an EGFR/ERBB2/JAK2 mutation for eligibility — it was withdrawn with zero enrollment, so no actual efficacy or safety signal exists yet. The supporting literature is likewise general (pediatric oncology review; a xenograft evaluation of a related EGFR/HER3-targeting combination), not Ewing-sarcoma-specific clinical evidence.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02689336 | Phase 2 | Withdrawn | 0 | Genomically-targeted pediatric basket trial combining erlotinib + temozolomide for relapsed/refractory solid tumors with EGFR/ERBB2/JAK2V617F mutations; withdrawn before enrollment, no outcome data generated. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 29080385 | 2018 | Cohort/Trial evaluation | Pediatric blood & cancer | Evaluated patritumab (anti-HER3) with/without erlotinib combined with standard cytotoxics (cisplatin, vincristine, cyclophosphamide) in pediatric sarcoma xenograft models expressing EGFR/HER3. |
| 26835334 | 2014 | Review | Translational pediatrics | General review of advances in pediatric cancer treatment; discusses risk-adapted therapy approaches, not Ewing-sarcoma/erlotinib-specific data. |
EU Market Information
Currently no EU marketing authorization records available (market_status: Not marketed / Not Marketed; total_licenses: 0).
Cytotoxicity
Erlotinib is classified here as antineoplastic based on its EGFR-TKI mechanism referenced in the repurposing rationale and cross-referenced literature (all predicted indications in this pack are oncology-related).
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (EGFR-TKI), not conventional cytotoxic chemotherapy |
| Myelosuppression Risk | Please refer to the SmPC warnings and precautions |
| Emetogenicity Classification | Please refer to the SmPC warnings and precautions |
| Monitoring Items | Please refer to the SmPC warnings and precautions |
| Handling Protection | Please refer to the SmPC warnings and precautions |
Safety Considerations
Please refer to the SmPC for safety information. (Key warnings, contraindications, and DDI data are all flagged as data gaps in this evidence pack — DG001, severity Blocking.)
Conclusion and Next Steps
Decision: Research Question (Decision Stage S1)
Rationale:
- Evidence level is L4 (mechanistic/preclinical only) — the sole related trial (NCT02689336) was withdrawn with zero enrollment, and the mechanistic link (EGFR/HER3 expression in a subset of Ewing sarcoma) is indirect since EWSR1-FLI1 fusion, not EGFR, is the primary disease driver.
To proceed, the following is needed:
- TFDA/SmPC full prescribing information (warnings, contraindications, DDI) — currently blocking (DG001), required before any S1 safety pre-assessment can proceed
- Complete mechanism of action (MOA) documentation (DG002)
- A newly enrolled, non-withdrawn clinical trial or biomarker-selected cohort in EGFR/HER3-expressing Ewing sarcoma to generate actual efficacy/safety signal
- EU/Taiwan regulatory and market status confirmation, since no licenses are currently on record for this drug
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.